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Rajan B, Abdelmoneim D, Salem AS, Belibasakis GN, Phemister R, Chen C, Coates D. Nanoencapsulation, biocompatibility and antibiofilm properties of chitosan/nisin Z spheres. Arch Oral Biol 2025; 173:106193. [PMID: 39970750 DOI: 10.1016/j.archoralbio.2025.106193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Revised: 01/25/2025] [Accepted: 02/09/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVES To study antibiofilm formation properties and biocompatibility of nisin Z for oral applications by encapsulating it in a highly muco-adhesive chitosan nanosphere and testing its effects against a multispecies biofilm and in vitro wound healing assay. MATERIALS AND METHODS Nisin Z was encapsulated in chitosan. Encapsulation parameters were evaluated using dynamic light scattering and visualised with microscopy. The effects on biofilm growth were tested using a Calgary biofilm device against a five species biofilm model. The effects on human gingival fibroblast (HGF) growth and migration were examined using an Idibi (500 nm gap) migration assay and the percentage of gap closure measured using ImageJ. RESULTS 20,000 IU/ml (0.525 mg/ml production concentration) nisin Z in a 1:40 ratio of TPP:chitosan produced optimal nanospheres with a low polydispersity index of 0.498 and average size of 264.8 nm. The freeze-dried nanospheres have a dose-dependent effect on biofilm formation, significantly reducing biofilm attachment compared to the positive control. No colonies were observed for chitosan/nisin Z nanospheres at > 6.25 mg/ml. HGFs in the control and 1000 IU nisin Z (unencapsulated) groups showed the most gap closure. The treatment group containing 50 mg/ml chitosan/nisin Z nanospheres showed gap closure comparable to the control. CONCLUSIONS Chitosan/nisin Z nanospheres were produced with antibiofilm activity with > 6.25 mg/ml nanospheres, while up to 50 mg/ml had no significant effect on HGF gap closure in vitro. Thus, nanoencapsulated nisin Z has potential as a therapeutic agent for the treatment of periodontitis.
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Affiliation(s)
- Bhavya Rajan
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Dina Abdelmoneim
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Amira Samir Salem
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Georgios N Belibasakis
- Division of Oral Health and Periodontology, Department of Dental Medicine, Karolinska Institute, Huddinge, Sweden
| | - Rebecca Phemister
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Chen Chen
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand
| | - Dawn Coates
- Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.
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Jonjaroen V, Jitrakorn S, Charoonnart P, Kaewsaengon P, Thinkohkaew K, Payongsri P, Surarit R, Saksmerprome V, Niamsiri N. Optimizing chitosan nanoparticles for oral delivery of double-stranded RNA in treating white spot disease in shrimp: Key insights and practical implications. Int J Biol Macromol 2025; 290:138970. [PMID: 39706429 DOI: 10.1016/j.ijbiomac.2024.138970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/11/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Delivering double-stranded RNA (dsRNA) in shrimp is challenging due to the lack of an effective carrier system. This study optimized chitosan nanoparticles (CNs) from two sources-α-chitosan from shrimp and β-chitosan from squid-to encapsulate antiviral dsRNA for oral administration via shrimp feed. Using response surface methodology (RSM), formulations were refined for encapsulation efficiency, particle size, polydispersity index, and zeta potential. Both types of CNs demonstrated high encapsulation efficiency (>95 %), small sizes (<300 nm), and stable zeta potential (>20 mV). Shrimp-derived CNs provided superior RNase protection and controlled release, while squid-derived CNs showed a burst release. Incorporated into feed, both types of CNs remained stable for over a month. Shrimp-derived CNs offered greater dsRNA protection (>70 %) and improved efficacy against white spot syndrome virus (WSSV), significantly reducing mortality. These results position shrimp-derived CNs as promising dsRNA carriers for combating WSSV in shrimp aquaculture.
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Affiliation(s)
- Veasarach Jonjaroen
- Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
| | - Sarocha Jitrakorn
- Center of Excellence for Shrimp Molecular Biology and Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; National Center of Genetic Engineering and Biotechnology, (BIOTEC), Thailand Science Park, Pathum Thani 12120, Thailand.
| | - Patai Charoonnart
- Center of Excellence for Shrimp Molecular Biology and Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; National Center of Genetic Engineering and Biotechnology, (BIOTEC), Thailand Science Park, Pathum Thani 12120, Thailand.
| | - Parichart Kaewsaengon
- Center of Excellence for Shrimp Molecular Biology and Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; National Center of Genetic Engineering and Biotechnology, (BIOTEC), Thailand Science Park, Pathum Thani 12120, Thailand.
| | - Korlid Thinkohkaew
- Department of Material Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
| | - Panwajee Payongsri
- Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
| | - Rudee Surarit
- Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand; Faculty of Dentistry, Siam University, Bangkok 10160, Thailand.
| | - Vanvimon Saksmerprome
- Center of Excellence for Shrimp Molecular Biology and Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; National Center of Genetic Engineering and Biotechnology, (BIOTEC), Thailand Science Park, Pathum Thani 12120, Thailand.
| | - Nuttawee Niamsiri
- Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
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Farid A, Mohamed A, Ahmed A, Mehanny F, Safwat G. Preparation of bee venom-loaded chitosan nanoparticles for treatment of streptozotocin-induced diabetes in male Sprague Dawley rats. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2024; 13:97. [DOI: 10.1186/s43088-024-00557-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/15/2024] [Indexed: 01/12/2025] Open
Abstract
Abstract
Background
Diabetes mellitus (DM) can be defined as an increase in the blood sugar level and a disturbance in protein, fat and carbohydrate metabolism. Bee venom (BV) is useful for treating and preventing diabetic rats’ histological and biochemical problems. Although the medical advantages of BV have been identified, its safety has remained a substantial barrier for its application. Consequently, the goal of our work was to prepare bee venom-loaded chitosan (BV-CS) nanoparticles (NPs), which would then be physically characterized. This was followed by examining the effect of the synthetized BV-CS NPs on oxidation, inflammation and coagulation in vitro. In diabetic rats’ model [induced by streptozotocin (STZ)], the produced BV-CS NPs were tested as an anti-diabetic medication.
Results
In vivo testing on pancreatic tissue homogenates showed that BV-CS NPs have antioxidant and anti-inflammatory properties. The results showed that BV-CS NPs can be used as a safe and efficient therapy for diabetes. Up to a concentration of 250 µg/ml, the generated NPs demonstrated potential antioxidant, membrane stabilizing, and non-cytotoxic capabilities. Our findings indicated that the administration of BV-CS NPs significantly controlled blood glucose levels and metabolic abnormalities that accompanied diabetes induction.
Conclusions
BV-CS NPs were successful in treating STZ-induced diabetes in rats, stimulated insulin secretion and were safe to be used in vivo.
Graphical abstract
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Singh P, Jayaraman G. Inhibition of the Naja naja venom toxicity by polymeric nanoparticles loaded with Leucas aspera methanolic extract. Front Pharmacol 2024; 15:1385213. [PMID: 38783952 PMCID: PMC11112068 DOI: 10.3389/fphar.2024.1385213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 04/22/2024] [Indexed: 05/25/2024] Open
Abstract
Background Snakebite is a neglected tropical disease that affects millions of people worldwide. Developing effective treatments can make a significant contribution to global health efforts and public health initiatives. To reduce mortality due to snakebite, there is an immediate need to explore novel and effective treatment methodologies. In that context, nanoparticle-based drug delivery is gaining a lot of attention. Hydrophilic nanoparticles are suitable for the delivery of therapeutic peptides, proteins, and antigens. Methods The present investigation is aimed at evaluating the anti-ophidian potential of the methanolic extract of the ethno-medicinal herb Leucas aspera (Willd.) loaded within chitosan nanoparticles (CNP-LA), against the Indian cobra (Naja naja) venom enzymes. For this purpose, nanoparticles were prepared using the ionic gelation method to enhance the efficacy of the extract. The physicochemical and structural features of nanoparticles were investigated using dynamic light scattering (DLS), Fourier-transform Infrared (FTIR), field emission scanning electron microscopy (FE-SEM), and X-ray diffraction (XRD) techniques. Results It was found that CNP-LA has an average size of 260 nm with a polydispersity index of 0.132 (PDI) and zeta potential of 34.7 mV, with an encapsulation efficiency of 92.46%. The in vitro release study was performed at pH 5.0 and 7.4. Furthermore, in vitro studies indicated that CNP-LA inhibited the phospholipase A2, hemolytic, and caseinolytic activities of Naja naja venom with the percentage inhibition of 92.5%, 83.9%, and 94.5%, respectively. Conclusion This is the first report on the application of herbal methanolic extract loaded within chitosan nanoparticles for neutralizing snake venom enzymes with increased efficiency.
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Affiliation(s)
| | - Gurunathan Jayaraman
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
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Darwish MM, Elneklawi MS, Mohamad EA. Aloe Vera coated Dextran Sulfate/Chitosan nanoparticles (Aloe Vera @ DS/CS) encapsulating Eucalyptus essential oil with antibacterial potent property. JOURNAL OF BIOMATERIALS SCIENCE, POLYMER EDITION 2022; 34:810-827. [PMID: 36369795 DOI: 10.1080/09205063.2022.2145869] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The goal of this work is to encapsulate Eucalyptus staigeriana essential oil in biopolymer matrices, to optimize the biological effects and the antibacterial properties of this oil. In this study, Eucalyptus extract was encapsulated in Aloe Vera coated Dextran Sulfate/Chitosan nanoparticles to form a hydrogel with potent properties. In this study, Eucalyptus extract was loaded on to Aloe Vera coated Dextran Sulphate/Chitosan nanoparticles to obtain a nano-hydrogel with potent properties. The characterization of nanoparticles was evaluated using transmission and scanning electron microscopes, dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry and antibacterial activity. The E. staigeriana release profile from the prepared nanoparticles was studied in vitro at a pH of 7.4. The results showed that this nano-carrier controls Eucalyptus release. Aloe Vera coated Dextran Sulfate/Chitosan nanoparticles encapsulated with E. staigeriana inhibited the bacteria by 47.27%. These investigations concluded that E. staigeriana loaded Aloe Vera coated Dextran Sulfate/Chitosan hydrogel could be used as a powerful dressing material to accelerate wound healing.
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Affiliation(s)
- Mirhane Mostafa Darwish
- Biophysics Department, Faculty of Science, Cairo University, Cairo University St., Giza, Egypt.
| | - Mona S Elneklawi
- Biomedical Equipment Department, Faculty of Applied Medical Sciences, October 6 University, 6th of October City, Giza, Egypt
| | - Ebtesam A Mohamad
- Biophysics Department, Faculty of Science, Cairo University, Cairo University St., Giza, Egypt.
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Joglekar AV, Dehari D, Anjum MM, Dulla N, Chaudhuri A, Singh S, Agrawal AK. Therapeutic potential of venom peptides: insights in the nanoparticle-mediated venom formulations. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2022. [DOI: 10.1186/s43094-022-00415-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Abstract
Background
Venoms are the secretions produced by animals, generally for the purpose of self-defense or catching a prey. Biochemically venoms are mainly composed of proteins, lipids, carbohydrates, ions, etc., and classified into three major classes, viz. neurotoxic, hemotoxic and cytotoxic based upon their mode of action. Venoms are composed of different specific peptides/toxins which are responsible for their unique biological actions. Though venoms are generally seen as a source of death, scientifically venom is a complex biochemical substance having a specific pharmacologic action which can be used as agents to diagnose and cure a variety of diseases in humans.
Main body
Many of these venoms have been used since centuries, and their specified therapies can also be found in ancient texts such as Charka Samhita. The modern-day example of such venom therapeutic is captopril, an antihypertensive drug developed from venom of Bothrops jararaca. Nanotechnology is a modern-day science of building materials on a nanoscale with advantages like target specificity, increased therapeutic response and diminished side effects. In the present review we have introduced the venom, sources and related constituents in brief, by highlighting the therapeutic potential of venom peptides and focusing more on the nanoformulations-based approaches. This review is an effort to compile all such report to have an idea about the future direction about the nanoplatforms which should be focused to have more clinically relevant formulations for difficult to treat diseases.
Conclusion
Venom peptides which are fatal in nature if used cautiously and effectively can save life. Several research findings suggested that many of the fatal diseases can be effectively treated with venom peptides. Nanotechnology has emerged as novel strategy in diagnosis, treatment and mitigation of diseases in more effective ways. A variety of nanoformulation approaches have been explored to enhance the therapeutic efficacy and reduce the toxicity and targeted delivery of the venom peptide conjugated with it. We concluded that venom peptides along with nanoparticles can evolve as the new era for potential treatments of ongoing and untreatable diseases.
Graphical Abstract
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Roque-Borda CA, Gualque MWDL, da Fonseca FH, Pavan FR, Santos-Filho NA. Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides. Pharmaceutics 2022; 14:891. [PMID: 35631477 PMCID: PMC9146920 DOI: 10.3390/pharmaceutics14050891] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/12/2022] [Accepted: 04/15/2022] [Indexed: 11/17/2022] Open
Abstract
Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.
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Affiliation(s)
- Cesar Augusto Roque-Borda
- Tuberculosis Research Laboratory, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil; (C.A.R.-B.); (F.R.P.)
| | - Marcos William de Lima Gualque
- Proteomics Laboratory, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil;
| | - Fauller Henrique da Fonseca
- Department of Biochemistry and Organic Chemistry, Chemistry Institute, São Paulo State University (UNESP), Araraquara 14800-903, Brazil;
| | - Fernando Rogério Pavan
- Tuberculosis Research Laboratory, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil; (C.A.R.-B.); (F.R.P.)
| | - Norival Alves Santos-Filho
- Department of Biochemistry and Organic Chemistry, Chemistry Institute, São Paulo State University (UNESP), Araraquara 14800-903, Brazil;
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Gao X, Liu N, Wang Z, Gao J, Zhang H, Li M, Du Y, Gao X, Zheng A. Development and Optimization of Chitosan Nanoparticle-Based Intranasal Vaccine Carrier. MOLECULES (BASEL, SWITZERLAND) 2021; 27:molecules27010204. [PMID: 35011436 PMCID: PMC8746444 DOI: 10.3390/molecules27010204] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/26/2021] [Accepted: 12/27/2021] [Indexed: 12/17/2022]
Abstract
Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.
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Affiliation(s)
| | | | | | | | | | | | - Yimeng Du
- Correspondence: (Y.D.); (X.G.); (A.Z.); Tel.: +86-010-6693-1694 or +86-135-2046-7936 (A.Z.)
| | - Xiang Gao
- Correspondence: (Y.D.); (X.G.); (A.Z.); Tel.: +86-010-6693-1694 or +86-135-2046-7936 (A.Z.)
| | - Aiping Zheng
- Correspondence: (Y.D.); (X.G.); (A.Z.); Tel.: +86-010-6693-1694 or +86-135-2046-7936 (A.Z.)
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Atashgahi M, Ghaemi B, Valizadeh A, Moshiri A, Nekoofar MH, Amani A. Epinephrine-entrapped chitosan nanoparticles covered by gelatin nanofibers: A bi-layer nano-biomaterial for rapid hemostasis. Int J Pharm 2021; 608:121074. [PMID: 34481888 DOI: 10.1016/j.ijpharm.2021.121074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 07/28/2021] [Accepted: 08/31/2021] [Indexed: 10/20/2022]
Abstract
Uncontrolled hemorrhage accounts for significant death risk both in trauma and surgery. Various bleeding control techniques have been emerged to augment hemostasis, which still has several limitations and drawbacks. In this study, epinephrine-entrapped chitosan nanoparticles were electrosprayed on a base pad and covered by a gelatin nanofiber layer (E-CS-Gl. Physico-chemical characteristics, hemocompatibility, cytotoxicity, and blood coagulation tests were studied in-vitro, and blood coagulation and hemostasis potential tests were performed in-vivo. The in-vitro results showed that the prepared nano-biomaterial is cytocompatible against HuGu cells. Also, hemocompatibility studies showed that PT and aPTT times did not change in comparison with the controls. Further blood coagulation study indicated that E-CS-Gl provides an ultimate interface to induce red blood cell absorption and aggregation, resulting in augmented blood coagulation. E-CS-Gl also caused rapid clotting in rat models of ruptured femoral artery and liver compared to controls. Findings exhibited that E-CS-Gl is a safe and effective hemostatic agent and provides a new approach for fast and safe hemorrhage control.
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Affiliation(s)
- Mahboubeh Atashgahi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, 1417755469 Tehran, Iran
| | - Behnaz Ghaemi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, 1417755469 Tehran, Iran
| | - Alireza Valizadeh
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences, 1417755469 Tehran, Iran
| | - Arfa Moshiri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 19857-17411 Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Mohammad Hossein Nekoofar
- Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences; School of Advanced Technologies in Medicine, Tehran University of Medical Sciences; Department of Endodontic, Bahçeşehir University School of Dentistry, İstanbul, Turkey.
| | - Amir Amani
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran; Medical Biomaterial Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Mirtajaddini SA, Fathi Najafi M, Vaziri Yazdi SA, Kazemi Oskuee R. Preparation of Chitosan Nanoparticles as a Capable Carrier for Antigen Delivery and Antibody Production. IRANIAN JOURNAL OF BIOTECHNOLOGY 2021; 19:e2871. [PMID: 35350645 PMCID: PMC8926316 DOI: 10.30498/ijb.2021.247747.2871] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Background Chitosan (CS) nanoparticles have attracted considerable attention as a non-viral and cationic carrier for delivery of therapeutic proteins and antigens and offer non-invasive routes of administration such as oral, nasal and ocular routes, and also show adjuvant characteristics for vaccines. Objectives Preparation and formulation of CS nanoparticles as a capable carrier with immunoadjuvant properties to enhance the bioavailability of antigen and produce antibody with high affinity. Materials and Methods CS nanoparticles were produced by ionic gelation process of sodium tripolyphosphate (TPP) with CS. Particle size and morphology of nanoparticles were determined using Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM) and also direct observation under light microscope. The influence of the initial BSA concentration and CS concentration on loading efficiency and release behavior was evaluated. The ε-toxin (derived from Clostridium perfringens type D) was loaded on CS nanoparticles and the complex was injected hypodermically into the rabbits for once. The anti ε-toxin antibody level in blood serum was evaluated using Dot Blot and ELISA methods. Results The CS nanoparticles in different groups have a particle diameter (Z-average) in approximate ranges of 200-400, 300-600, 450-800 nm and a positive Zeta potential (32.4 - 48.6 mv). Optimum loading efficiency was achieved for CS at a concentration of 0.5 mg.mL-1 and TPP of 1.0 mg.mL-1. The results showed that the toxin-CS complex produces antitoxin at levels more than twice as high the control. Conclusion The CS nanoparticles can be used as a good biodegradable carrier for protein and antigen delivery.
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Affiliation(s)
| | - Mohsen Fathi Najafi
- Razi Vaccine and Serum Research Institute. Mashhad Branch, Agricultural Research, Education and Extension Organization (AREEO), Mashhad, Khorasan Razavi, Iran
| | - Seyed Ali Vaziri Yazdi
- Department of Chemical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Reza Kazemi Oskuee
- Depatment of Modern Sciences and Technologies, School of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Proença-Assunção JDC, Farias-de-França AP, Tribuiani N, Cogo JC, Collaço RDC, Randazzo-Moura P, Consonni SR, Chaud MV, Dos Santos CA, Oshima-Franco Y. The Influence of Silver Nanoparticles Against Toxic Effects of Philodryas olfersii Venom. Int J Nanomedicine 2021; 16:3555-3564. [PMID: 34079248 PMCID: PMC8164871 DOI: 10.2147/ijn.s293366] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 04/27/2021] [Indexed: 12/31/2022] Open
Abstract
Purpose A silver nanoparticle obtained by reducing salts with solid dispersion of curcumin (130 nm, 0.081 mg mL−1) was used to counteract against the toxic – edematogenic, myotoxic, and neurotoxic – effects of Philodryas olfersii venom. Methods The edematogenic effect was evaluated by plasma extravasation in rat dorsal skin after injection of 50 µg per site of venom alone or preincubated with 1, 10, and 100 µL of AgNPs; the myotoxicity was evaluated by measuring the creatine kinase released into the organ-bath before the treatment and at the end of each experiment; and neurotoxicity was evaluated in chick biventer cervicis using the conventional myographic technique, face to the exogenous acetylcholine (ACh) and potassium chloride (KCl) added into the bath before the treatment and after each experiment. Preliminarily, a concentration-response curve of AgNPs was carried out to select the concentration to be used for neutralizing assays, which consists of neutralizing the venom-induced neuromuscular paralysis and edema by preincubating AgNPs with venom for 30 min. Results The P. olfersii venom-induced edema (n=6) and a complete neuromuscular blockade (n=4) that includes the total and unrecovered block of ACh and KCl contractures. AgNPs produced a concentration-dependent decrease the venom-induced edema (n=6) from 223.3% to 134.4% and to 100.5% after 10 and 100 µL AgNPs-preincubation, respectively. The preincubation of venom with AgNPs (1 µL; n=6) was able to maintain 46.5 ± 10.9% of neuromuscular response under indirect stimuli, 39.2 ± 9.7% of extrinsic nicotinic receptors functioning in absence of electrical stimulus and 28.3 ± 8.1% of responsiveness to potassium on the sarcolemmal membrane. The CK release was not affected by any experimental protocol which was like control. Conclusion AgNPs interact with constituents of P. olfersii venom responsible for the edema-forming activity and neuromuscular blockade, but not on the sarcolemma membrane-acting constituents. The protective effect of the studied AgNPs on avian preparation points out to molecular targets as intrinsic and extrinsic nicotinic receptors.
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Affiliation(s)
| | | | - Natalia Tribuiani
- Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (Uniso), Sorocaba, SP, Brazil
| | - Jose Carlos Cogo
- Bioengineering and Biomedical Engineering Programs, Technological and Scientific Institute, Brazil University, São Paulo, Brazil
| | - Rita de Cássia Collaço
- Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil
| | - Priscila Randazzo-Moura
- Department of Surgery, Pontifícia Universidade Católica De São Paulo (PUCSP), Sorocaba, SP, Brazil
| | - Sílvio Roberto Consonni
- Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil
| | - Marco Vinicius Chaud
- Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (Uniso), Sorocaba, SP, Brazil
| | | | - Yoko Oshima-Franco
- Post-Graduate Program in Pharmaceutical Sciences, University of Sorocaba (Uniso), Sorocaba, SP, Brazil
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Sasidharan AP, Meera V, Raphael VP. Investigations on characteristics of polyurethane foam impregnated with nanochitosan and nanosilver/silver oxide and its effectiveness in phosphate removal. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:12980-12992. [PMID: 33097998 DOI: 10.1007/s11356-020-11257-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 10/13/2020] [Indexed: 06/11/2023]
Abstract
A novel potential adsorbent, produced with chitosan nanoparticles and silver/silver oxide nanoparticles impregnated on polyurethane foam (PFCA), is developed for phosphate removal in aqueous solutions. The ultraviolet-visible (UV-Vis) spectroscopy uncovered the emergence of nanoparticles. The field emission scanning electron microscopy (FESEM) provided the mean size of chitosan nanoparticles between 56 and 112 nm and that of silver-silver oxide nanoparticles between 44 and 75 nm. Energy dispersive X-ray (EDX) spectroscopy determined the presence of specific elements (C, O, P and Ag) in the adsorbent before and after treatment. Fourier transform infrared (FTIR) spectroscopy revealed the interplay between the N-H bond of amino group in PFCA and phosphate ions during adsorption. X-ray diffraction (XRD) analysis of PFCA showed nearly the same pattern before and after treatment, indicating the stability of PFCA. The silver ion concentration in the effluent from inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis was found to be very less and below the drinking water limits. The surface area estimated by Brunauer-Emmett-Teller (BET) studies was found to be 2.17 m2/g. The experimental studies showed that PFCA can remove 61.24% of phosphate from an influent phosphate phosphorus concentration of 50 mg P/L, at its propitious condition. Even after 7 cycles of reuse, PFCA proved to be effective in removing 20.58% of phosphate. Hence, PFCA can be considered to be a potential sorbent for removing phosphate from surface water. Graphical abstract.
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Affiliation(s)
- Anjali P Sasidharan
- Department of Civil Engineering, Government Engineering College, Thrissur, APJ Adbul Kalam Technological University, Thiruvananthapuram, Kerala, India
| | - V Meera
- Department of Civil Engineering, Government Engineering College, Thrissur, APJ Adbul Kalam Technological University, Thiruvananthapuram, Kerala, India.
| | - Vinod P Raphael
- Department of Chemistry, Government Engineering College, Thrissur, APJ Adbul Kalam Technological University, Thiruvananthapuram, Kerala, India
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Chogale MM, Gaikwad SS, Kulkarni SP, Patravale VB. Quality-by-design Enabled Chitosan Nanoparticles for Antitubercular Therapy: Formulation, Statistical Optimization, and In Vitro Characterization. CURRENT DRUG THERAPY 2021. [DOI: 10.2174/1574885515666200722150305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Tuberculosis (TB) continues to be among the leading causes of high mortality
among developing countries. Though a seemingly effective treatment regimen against TB is
in place, there has been no significant improvement in the therapeutic rates. This is primarily owing
to the high drug doses, their associated side-effects, and prolonged treatment regimen. Discontinuation
of therapy due to the severe side effects of the drugs results in the progression of the infection
to the more severe drug-resistant TB.
Objectives:
Reformulation of the current existing anti TB drugs into more efficient dosage forms
could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic,
high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a
first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration.
Methods:
INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic
crosslinker. Drug-excipient compatibility was evaluated using DSC and FT-IR. The formulation
was optimized on the principles of Quality-by-Design using a full factorial design.
Results:
The obtained nanoparticles were spherical in shape having an average size of 620±10.97
nm and zeta potential +16.87±0.79 mV. Solid-state characterization revealed partial encapsulation
and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended
release of INH from the system. In vitro cell line-based safety and efficacy studies revealed
satisfactory results.
Conclusion:
The developed nanosystem is thus an efficient approach for antitubercular therapy.
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Affiliation(s)
- Manasi M. Chogale
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (East), Mumbai-400 019,India
| | - Sujay S. Gaikwad
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annex, E. Borges Marg, Parel, Mumbai-400 012, Maharashtra,India
| | - Savita P. Kulkarni
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annex, E. Borges Marg, Parel, Mumbai-400 012, Maharashtra,India
| | - Vandana B. Patravale
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (East), Mumbai-400 019,India
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Wang J, Chin D, Poon C, Mancino V, Pham J, Li H, Ho PY, Hallows KR, Chung EJ. Oral delivery of metformin by chitosan nanoparticles for polycystic kidney disease. J Control Release 2021; 329:1198-1209. [PMID: 33127449 PMCID: PMC7904655 DOI: 10.1016/j.jconrel.2020.10.047] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 10/20/2020] [Accepted: 10/22/2020] [Indexed: 12/15/2022]
Abstract
Nanoparticle drug delivery has many advantages over small molecule therapeutics, including reducing off-target side effects and increasing drug potency. However, many nanoparticles are administered parenterally, which is challenging for chronic diseases such as polycystic kidney disease (PKD), the most common hereditary disease worldwide in which patients need continuous treatment over decades. To address this clinical need, we present the development of nanoparticles synthesized from chitosan, a widely available polymer chosen for its ability to improve oral bioavailability. Specifically, we optimized the synthesis parameters of chitosan nanoparticles and demonstrate mucoadhesion and permeation across an intestinal barrier model in vitro. Furthermore, when administered orally to mice, ex vivo imaging of rhodamine-loaded chitosan nanoparticles showed significantly higher accumulation in the intestines compared to the free model drug, as well as 1.3 times higher serum area under the curve (AUC), demonstrating controlled release and improved serum delivery over 24 h. To test its utility for chronic diseases such as PKD, we loaded the candidate PKD drug, metformin, into chitosan nanoparticles, and upon oral administration to a PKD murine model (Pkd1fl/fl;Pax8-rtTA;Tet-O cre), a lower cyst burden was observed compared to free metformin, and was well tolerated upon repeated dosages. Blood urea nitrogen (BUN) and creatinine levels were similar to untreated mice, demonstrating kidney and biocompatibility health. Our study builds upon previous chitosan-based drug delivery approaches, and demonstrates a novel, oral nanoformulation for PKD.
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Affiliation(s)
- Jonathan Wang
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
| | - Deborah Chin
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
| | - Christopher Poon
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
| | - Valeria Mancino
- Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; USC/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Jessica Pham
- Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; USC/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Hui Li
- Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; USC/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Pei-Yin Ho
- Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; USC/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Kenneth R Hallows
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; USC/UKRO Kidney Research Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Eun Ji Chung
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA; Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Bridge Institute, University of Southern California, Los Angeles, CA, USA.
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15
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Oksal E, Pangestika I, Muhammad TST, Mohamad H, Amir H, Kassim MNI, Andriani Y. In vitro and in vivo studies of nanoparticles of chitosan- Pandanus tectorius fruit extract as new alternative treatment for hypercholesterolemia via Scavenger Receptor Class B type 1 pathway. Saudi Pharm J 2020; 28:1263-1275. [PMID: 33132720 PMCID: PMC7584805 DOI: 10.1016/j.jsps.2020.08.017] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 08/25/2020] [Indexed: 12/11/2022] Open
Abstract
Pandanus tectorius fruit, a natural product rich in tangeretin and ethyl caffeate, has been reported to have potential as anti-hypercholesterolemia agent via Scavenger Receptor Class B type 1 (SR-B1) pathway. However, due to its semi-polar properties, P. tectorius extract exhibits poor solubility when used as a medical remedy. The extract’s solubility can potentially be improved through a synthesis of nanoparticles of chitosan-P. tectorius fruit extract. This can also increase the extract’s SR-B1 gene expression activity. To date, no studies of nanoparticles of chitosan-P. tectorius fruit extract and its pathway via SR-B1 have been published anywhere. In this study, cytotoxicity properties against HepG2 were explored by MTT. Then luciferase assay was used to detect their effectiveness in increasing SR-B1 activity. An in vivo study using Sprague dawley was carried out to observe the extract nanoparticles’ effectiveness in reducing the cholesterol levels and the toxicity property in rat’s liver. As the results showed, the extract nanoparticles had no cytotoxic activity against HepG2 cells and exhibited higher SR-B1 gene expression activity than the non-nanoparticle form. As the in vivo study proved, nanoparticle treatment can reduce the levels of TC (197%), LDL (360%), and TG (109%), as well as increase the level of HDL cholesterol by 150%, in comparison to those for the untreated high-cholesterol diet group. From the toxicity study, it was found that there was non-toxicity in the liver. It can be concluded that nanoparticles of chitosan-P. tectorius fruit extract successfully increased P. tectorius fruit extract’s effectiveness in reducing hypercholesterolemia via SR-B1 pathway. Hence, it can be suggested that nanoparticles of chitosan-P. tectorius fruit extract is safe and suitable as an alternative treatment for controlling hypercholesterolemia via SR-B1 pathway.
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Affiliation(s)
- Efriyana Oksal
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
| | - Inten Pangestika
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
| | - Tengku Sifzizul Tengku Muhammad
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
- Research Management Center, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
| | - Habsah Mohamad
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
| | - Hermansyah Amir
- Educational Chemistry Program, Faculty of Teacher Training and Education, Bengkulu University, Bengkulu 38371, Indonesia
| | - Murni Nur Islamiah Kassim
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
| | - Yosie Andriani
- Institute of Marine Biotechnology, Universiti Malaysia Terengganu, Mengabang Telipot 21030, Kuala Nerus, Terengganu, Malaysia
- Corresponding author.
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Han Y, Tang J, Xia J, Wang R, Qin C, Liu S, Zhao X, Chen H, Lin Q. Anti-Adhesive And Antiproliferative Synergistic Surface Modification Of Intraocular Lens For Reduced Posterior Capsular Opacification. Int J Nanomedicine 2019; 14:9047-9061. [PMID: 31819418 PMCID: PMC6875265 DOI: 10.2147/ijn.s215802] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 10/30/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Posterior capsular opacification (PCO) is the main complication after intraocular lens (IOL) implantation in cataract surgery, which is the result of lens epithelial cell (LEC) adhesion, proliferation and migration on the IOL and at the lens capsule interface. Hydrophilic surface modification, such as surface heparinization, decreases the cell adhesion, which has been commercialized and used clinically. However, clinical long-term observation results show no significant difference between the pristine and heparinized IOLs. METHODS To prevent PCO over the long time span, we modified the IOLs with an antiproliferative drug-loaded hydrophilic coating. The antiproliferative drug doxorubicin (DOX)-incorporated chitosan (CHI) nanoparticle was fabricated by sodium tripolyphosphate (TPP) gelation. Such antiproliferative drug-loaded CHI-TPP-DOX nanoparticles (CTDNP) were used as one of the building blocks to prepare polyelectrolyte multilayer with heparin (HEP) via layer-by-layer assembly, obtaining (HEP/CTDNP)n multilayers. The assembly process was characterized by quartz crystal microbalance with dissipation (QCM-D). The drug release behavior of the coating was investigated by ultra-HPLC (UPLC). In vitro cell experiments were carried out to monitor the effects of multifunctional coatings on cellular adhesion, proliferation and migration. And the intraocular implantation was performed on rabbits to evaluate the in vivo PCO inhibitory effect of such surface-functionalized IOLs. RESULTS The positively charged CTDNP was successfully prepared by ionic gelation. The QCM-D results indicate the successful preparation of the (HEP/CTDNP)n multilayer film. Drug release profiles showed that surface-multifunctionalized IOL had drug-sustained release properties. In vitro cell culture results showed significant inhibition of adhesion, proliferation and migration of LECs after surface modification. The in vivo results showed that the IOLs with multifunctionalized surface can effectively reduce the posterior hyperplasia and Soemmering's ring (SR) formation. CONCLUSION These findings suggested that such multifunctionalized drug-eluting IOLs can effectively reduce the posterior hyperplasia and SR formation when intraocular implantation has a major impact on reducing PCO incidence. Thus they have a great potential in improving patient vision recovery and maintenance.
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Affiliation(s)
- Yuemei Han
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Junmei Tang
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Jiayi Xia
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Rui Wang
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Chen Qin
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Sihao Liu
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Xia Zhao
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
| | - Hao Chen
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
- Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou32500, People’s Republic of China
| | - Quankui Lin
- School of Ophthalmology & Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou325027, People’s Republic of China
- Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou32500, People’s Republic of China
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Dedloff MR, Effler CS, Holban AM, Gestal MC. Use of Biopolymers in Mucosally-Administered Vaccinations for Respiratory Disease. MATERIALS 2019; 12:ma12152445. [PMID: 31370286 PMCID: PMC6695719 DOI: 10.3390/ma12152445] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/23/2019] [Accepted: 07/28/2019] [Indexed: 12/20/2022]
Abstract
Communicable respiratory infections are the cause of a significant number of infectious diseases. The introduction of vaccinations has greatly improved this situation. Moreover, adjuvants have allowed for vaccines to be more effective with fewer adverse side effects. However, there is still space for improvement because while the more common injected formulations induce a systematic immunity, they do not confer the mucosal immunity needed for more thorough prevention of the spread of respiratory disease. Intranasal formulations provide systemic and mucosal immune protection, but they have the potential for more serious side effects and a less robust immune response. This review looks at seven different adjuvants—chitosan, starch, alginate, gellan, β-glucan, emulsan and hyaluronic acid—and their prospective ability to improve intranasal vaccines as adjuvants and antigen delivery systems.
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Affiliation(s)
| | - Callie S Effler
- Department of Natural Sciences and Mathematics, College of Arts and Sciences, Lee University, Cleveland, TN 37311, USA
| | - Alina Maria Holban
- Department of Microbiology, Faculty of Biology, University of Bucharest, 030018 Bucuresti, Romania
- Research Institute of the University of Bucharest (ICUB), 050107 Bucharest, Romania
- Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Polizu Street, 011061 Bucharest, Romania
| | - Monica C Gestal
- Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
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18
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Dos Santos AP, de Araújo TG, Rádis-Baptista G. Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications. Curr Pharm Biotechnol 2019; 21:97-109. [PMID: 31223083 DOI: 10.2174/1389201020666190621104624] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 04/17/2019] [Accepted: 05/08/2019] [Indexed: 12/30/2022]
Abstract
Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.
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Affiliation(s)
- Ana P Dos Santos
- Program of Post-graduation in Pharmaceutical Sciences (FFEO/UFC), Federal University of Ceara, Ceara, Brazil
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Biodegradable cross-linked chitosan nanoparticles improve anti-Candida and anti-biofilm activity of TistH, a peptide identified in the venom gland of the Tityus stigmurus scorpion. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 103:109830. [PMID: 31349502 DOI: 10.1016/j.msec.2019.109830] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/15/2019] [Accepted: 05/29/2019] [Indexed: 12/19/2022]
Abstract
Among several bioactive peptides identified from the venom glands of the Tityus stigmurus scorpion, one peptide with hypotensive action (TistH, Tityus stigmurus Hypotensin) showed multifunctional and biotechnological applications. The maximum efficacy of this class of compounds can be achieved by immobilizing it in specific and suitable biomaterials or suitable carriers. In this study, distinct entrapment methods of TistH in chitosan nanoparticles was tested using its incorporation (CN-TistH-Inc) or adsorption (CN-TistH-Ads) methods by ionotropic gelification. Physico-chemical properties as well as biocompatibility and antifungal efficacy were assessed for different samples. Atomic force microscopy and field emission gun scanning electronic microscopy images associated with particle size measurements demonstrated that the two methods induced cationic spherical, small (< 160 nm), and narrow-sized (PdI about 0.3) nanoparticles, even after peptide loading greater than 96.5%, which was confirmed using Fourier transform infrared spectroscopy. The colloidal suspensions showed to be stable for 8 weeks and were able to induce the desired slow in vitro peptide release. Cytotoxicity assays performed in normal cells originated from murine macrophages (RAW 264.7) and kidneys of African green monkeys (Vero E6) suggested biocompatibility of samples. The CN-TistH-Inc and CN-TistH-Ads showed a minimal inhibitory concentration of 89.2 μg.mL-1 against Candida albicans, 11.1 μg.mL-1 for C. parapsilosis and C. tropicalis, confirmed by minimum fungicidal concentrations assay. Moreover, the TistH-loaded cross-linked chitosan nanoparticles significantly reduced the biofilm formation of clinical yeast sepsis of C. tropicalis and C. krusei, as well as clinical yeasts of vulvovaginal candidiasis of C. albicans. In this approach, biodegradable nanocarriers prepared using simple and reproducible methods demonstrated the ability to deliver the TistH peptide from T. stigmurus and improve its antifungal efficacy.
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20
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Development of a photoresponsive chitosan conjugated prodrug nano-carrier for controlled delivery of antitumor drug 5-fluorouracil. Int J Biol Macromol 2019; 121:1070-1076. [DOI: 10.1016/j.ijbiomac.2018.10.095] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 10/01/2018] [Accepted: 10/14/2018] [Indexed: 10/28/2022]
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21
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Gláucia-Silva F, Torres-Rêgo M, Rocha Soares KS, Damasceno IZ, Tambourgi DV, Silva-Júnior AAD, Fernandes-Pedrosa MDF. A biotechnological approach to immunotherapy: Antivenom against Crotalus durissus cascavella snake venom produced from biodegradable nanoparticles. Int J Biol Macromol 2018; 120:1917-1924. [PMID: 30287370 DOI: 10.1016/j.ijbiomac.2018.09.203] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 08/20/2018] [Accepted: 09/28/2018] [Indexed: 12/22/2022]
Abstract
Snakebite envenoming is a tropical disease neglected worldwide. In Brazil, the Crotalus durissus cascavella (CDC) snake belongs to a genus with venom of highest lethality. A search for new immunoadjuvants aimed to expand the therapeutic alternatives to improve vaccines and antivenom. This approach proposed to produce small and narrow-sized cationic CDC venom-loaded chitosan nanoparticles (CHNP) able to induce antibody response against the CDC venom. The ionic gelation method induced the formation of stable and slightly smooth spherical nanoparticles (<160 nm) with protein loading efficiency superior to 90%. The interactions between venom proteins and CHNP assessed using FT-IR spectroscopy corroborated with the in vitro release behavior of proteins from nanoparticles. Finally, the immunization animal model using BALB/c mice demonstrated the higher effectiveness of CDC venom-loaded CHNP compared to aluminum hydroxide, a conventional immunoadjuvant. Thus, CHNPs loaded with CDC venom exhibited a promising biotechnological approach to immunotherapy.
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Affiliation(s)
- Fiamma Gláucia-Silva
- Graduate Program on Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil.
| | - Manoela Torres-Rêgo
- Graduate Program on Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil.
| | - Karla Samara Rocha Soares
- Graduate Program on Biochemistry, Bioscience Center, University Campus, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova, 59072-970 Natal, Brazil.
| | - Igor Zumba Damasceno
- Department of Materials Engineering, Technology Center, University Campus, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova, 59078-970 Natal, Brazil.
| | - Denise Vilarinho Tambourgi
- Laboratory of Immunochemistry, Instituto Butantan, Avenida Vital Brasil, 1500, Instituto Butantan, São Paulo 05503-000, Brazil.
| | - Arnóbio Antônio da Silva-Júnior
- Graduate Program on Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil.
| | - Matheus de Freitas Fernandes-Pedrosa
- Graduate Program on Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil; Graduate Program on Biochemistry, Bioscience Center, University Campus, Federal University of Rio Grande do Norte, Avenida Senador Salgado Filho, 3000, Lagoa Nova, 59072-970 Natal, Brazil.
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Anand M, Sathyapriya P, Maruthupandy M, Hameedha Beevi A. Synthesis of chitosan nanoparticles by TPP and their potential mosquito larvicidal application. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.flm.2018.07.003] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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23
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Soares KSR, Gláucia-Silva F, Daniele-Silva A, Torres-Rêgo M, Araújo NKD, Menezes YASD, Damasceno IZ, Tambourgi DV, da Silva-Júnior AA, Fernandes-Pedrosa MDF. Antivenom Production against Bothrops jararaca and Bothrops erythromelas Snake Venoms Using Cross-Linked Chitosan Nanoparticles as an Immunoadjuvant. Toxins (Basel) 2018; 10:toxins10040158. [PMID: 29659491 PMCID: PMC5923324 DOI: 10.3390/toxins10040158] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 04/03/2018] [Accepted: 04/05/2018] [Indexed: 12/17/2022] Open
Abstract
In Brazil, envenomation by snakes of the genus Bothrops is clinically relevant, particularly for the species Bothrops jararaca and B. erythromelas. The most effective treatment for envenomation by snakes is the administration of antivenoms associated with adjuvants. Novel adjuvants are required to reduce side effects and maximize the efficiency of conventional serum and vaccine formulations. The polymer chitosan has been shown to have immunoadjuvant properties, and it has been used as a platform for delivery systems. In this context, we evaluated the potential immunoadjuvant properties of chitosan nanoparticles (CNPs) loaded with B. jararaca and B. erythromelas venoms in the production of sera against these venoms. Stable CNPs were obtained by ionic gelation, and mice were immunized subcutaneously for 6 weeks with 100 µL of each snake venom at concentrations of 5.0 or 10.0% (w/w), encapsulated in CNPs or associated with aluminium hydroxide (AH). The evaluation of protein interactions with the CNPs revealed their ability to induce antibody levels equivalent to those of AH, even with smaller doses of antigen. In addition, the CNPs were less inflammatory due to their modified release of proteins. CNPs provide a promising approach for peptide/protein delivery from snake venom and will be useful for new vaccines.
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Affiliation(s)
- Karla Samara Rocha Soares
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Fiamma Gláucia-Silva
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Alessandra Daniele-Silva
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Manoela Torres-Rêgo
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Nathália Kelly de Araújo
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Yamara Arruda Silva de Menezes
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
| | - Igor Zumba Damasceno
- Department of Materials Engineering, Technology Center, University Campus, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil.
| | | | - Arnóbio Antônio da Silva-Júnior
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
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Mahdizadeh Barzoki Z, Emam-Djomeh Z, Mortazavian E, Rafiee-Tehrani N, Behmadi H, Rafiee-Tehrani M, Moosavi-Movahedi AA. Determination of diffusion coefficient for released nanoparticles from developed gelatin/chitosan bilayered buccal films. Int J Biol Macromol 2018; 112:1005-1013. [PMID: 29408415 DOI: 10.1016/j.ijbiomac.2018.01.215] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2017] [Revised: 01/21/2018] [Accepted: 01/31/2018] [Indexed: 01/23/2023]
Abstract
This study aims at the mathematical optimization by Box-Behnken statistical design, fabrication by ionic gelation technique and in vitro characterization of insulin nanoparticles containing thiolated N- dimethyl ethyl chitosan (DMEC-Cys) conjugate. Then Optimized insulin nanoparticles were loaded into the buccal film, and in-vitro drug release from films was investigated, and diffusion coefficient was predicted. The optimized nanoparticles were shown to have mean particle size diameter of 148nm, zeta potential of 15.5mV, PdI of 0.26 and AE of 97.56%. Cell viability after incubation with optimized nanoparticles and films were assessed using an MTT biochemical assay. In vitro release study, FTIR and cytotoxicity also indicated that nanoparticles made of this thiolated polymer are suitable candidates for oral insulin delivery.
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Affiliation(s)
- Zahra Mahdizadeh Barzoki
- Transfer Phenomena Laboratory (TPL), Department of Food Science, Technology and Engineering, Faculty of Agricultural Engineering and Technology, College of Agriculture and Natural Resources, University of Tehran, PO Box: 4111, 31587-11167 Karaj, Iran
| | - Zahra Emam-Djomeh
- Transfer Phenomena Laboratory (TPL), Department of Food Science, Technology and Engineering, Faculty of Agricultural Engineering and Technology, College of Agriculture and Natural Resources, University of Tehran, PO Box: 4111, 31587-11167 Karaj, Iran; Center of Excellence for Application of Modern Technologies for Producing Functional Foods and Drinks, Iran.
| | | | | | - Homa Behmadi
- Agricultural Engineering Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
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Ma Z, Garrido-Maestu A, Jeong KC. Application, mode of action, and in vivo activity of chitosan and its micro- and nanoparticles as antimicrobial agents: A review. Carbohydr Polym 2017; 176:257-265. [DOI: 10.1016/j.carbpol.2017.08.082] [Citation(s) in RCA: 155] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 07/28/2017] [Accepted: 08/18/2017] [Indexed: 01/22/2023]
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Pavez L, Tobar N, Chacón C, Arancibia R, Martínez C, Tapia C, Pastor A, González M, Martínez J, Smith PC. Chitosan-triclosan particles modulate inflammatory signaling in gingival fibroblasts. J Periodontal Res 2017; 53:232-239. [DOI: 10.1111/jre.12510] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/01/2017] [Indexed: 11/30/2022]
Affiliation(s)
- L. Pavez
- Laboratory of Molecular Biology, Institute of Nutrition and Technology; University of Chile; Santiago RM Chile
| | - N. Tobar
- Laboratory of Cell Biology, Institute of Nutrition and Food Technology; University of Chile; Santiago RM Chile
| | - C. Chacón
- Laboratory of Molecular Biology, Institute of Nutrition and Technology; University of Chile; Santiago RM Chile
| | - R. Arancibia
- Dentistry, Faculty of Medicine; Pontificia Universidad Católica de Chile; Santiago RM Chile
| | - C. Martínez
- Dentistry, Faculty of Medicine; Pontificia Universidad Católica de Chile; Santiago RM Chile
| | - C. Tapia
- Faculty of Chemical and Pharmaceutical Sciences; University of Chile; Santiago RM Chile
| | - A. Pastor
- Department of Sciences, Chemistry Section; Pontificia Universidad Católica del Peru; Lima Peru
| | - M. González
- Laboratory of Molecular Biology, Institute of Nutrition and Technology; University of Chile; Santiago RM Chile
- Bioinformatics and Gene Expression, Institute of Nutrition and Food Technology; University of Chile and Center for Genome Regulation, University of Chile; Santiago RM Chile
| | - J. Martínez
- Laboratory of Cell Biology, Institute of Nutrition and Food Technology; University of Chile; Santiago RM Chile
| | - P. C. Smith
- Dentistry, Faculty of Medicine; Pontificia Universidad Católica de Chile; Santiago RM Chile
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Delivery of viral recombinant VP28 protein using chitosan tripolyphosphate nanoparticles to protect the whiteleg shrimp, Litopenaeus vannamei from white spot syndrome virus infection. Int J Biol Macromol 2017; 107:1131-1141. [PMID: 28951305 DOI: 10.1016/j.ijbiomac.2017.09.094] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 09/20/2017] [Accepted: 09/22/2017] [Indexed: 11/22/2022]
Abstract
The VP28 gene of white spot syndrome virus was amplified by PCR using gene specific primer set and cloned into pRSET B vector to produce recombinant VP28 (r-VP28) in E. coli GJ1158. The chitosan tripolyphosphate nanoparticles (CS/TPP) were prepared by ionic gelation process and characterized. The purified r-VP28 protein was encapsulated by CS/TPP nanoparticles. The encapsulation efficiency of CS/TPP nanoparticles was found to be 84.8% for r-VP28 protein binding with CS/TPP nanoparticles. The in vitro release profile of encapsulated r-VP28 was determined after treating with protease and chitosanase. The different types of feed were formulated and named as normal feed with PBS, Feed A coated with crude r-VP28, Feed B with purified r-VP28 and Feed C with CS/TPP encapsulated r-VP28 (Purified). Tissue distribution and clearance of r-VP28 at different time intervals were examined in shrimp fed with different types of feed by ELISA and the results showed the presence of r-VP28 protein in different organs. Various immunological parameters were assessed in experimental shrimp. The mRNA expression of five immune-related genes was analysed by qPCR in order to investigate their response to all types of feed in shrimp. A cumulative percentage mortality was also recorded in treated shrimp challenged with WSSV.
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28
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Self-assembled scorpion venom proteins cross-linked chitosan nanoparticles for use in the immunotherapy. J Mol Liq 2017. [DOI: 10.1016/j.molliq.2017.06.071] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Raphaël KJ, Meimandipour A. Antimicrobial Activity of Chitosan Film Forming Solution Enriched with Essential Oils; an in Vitro Assay. IRANIAN JOURNAL OF BIOTECHNOLOGY 2017; 15:111-119. [PMID: 29845058 DOI: 10.15171/ijb.1360] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Revised: 07/02/2016] [Accepted: 06/19/2017] [Indexed: 11/09/2022]
Abstract
Background: The resistance of the bacteria and fungi to the innumerous antimicrobial agents is a major challenge in the treatment of the infections demands to the necessity for searching and finding new sources of substances with antimicrobial properties. The incorporation of the essential oils (EOs) in chitosan film forming solution may enhance antimicrobial properties. However, its use as the feeding additive in the poultry nutrition needs to clarify the product's activity against both pathogen and the useful microbes in the gastrointestinal tract. Objectives: In the present study, we carried out an in vitro investigation and evaluated the antimicrobial activity of chitosan film forming solution incorporated with essential oils (CFs+EOs) against microbial strains including Staphylococcus aureus, Escherichia coli, Enterococcus faecium, Lactobacillus rahmnosus, Aspergillus niger and Alternaria alternate. Material and Methods: In three replicates, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of different treatments including: 1- essential oils (EOs), 2- chitosan film solution (CFs), and 3-chitosan film solution enriched with EOs (CFs+EOs) were determined against above mentioned microbes. Results: The results indicated that the chitosan solution enriched with essential oils (CFs+EOs) is capable of inhibiting the bacterial and fungal growth even at the lowest concentrations. The MIC and MBC for all the antimicrobial agents against Escherichia coli and Staphylococcus aureus were very low compared to the concentrations needed to inhibit the growth of useful bacteria, Lactobacillus rahmnosu and Enterococcus faecium. The antifungal activity of chitosan was enhanced as the concentration of EOs increased in the film solution. Conclusion: Chitosan-EOs complexes are the promising candidate for novel contact antimicrobial agents that can be used in animal feeds.
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Affiliation(s)
- Kana Jean Raphaël
- Department of Animal Productions, Faculty of Agronomy and Agricultural Sciences, University of Dschang, 70 Dschang, Cameroon
| | - Amir Meimandipour
- Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, 14965/161, Iran
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Manchanda S, Sahoo PK. Topical delivery of acetazolamide by encapsulating in mucoadhesive nanoparticles. Asian J Pharm Sci 2017; 12:550-557. [PMID: 32104368 PMCID: PMC7032124 DOI: 10.1016/j.ajps.2017.04.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 04/27/2017] [Indexed: 01/20/2023] Open
Abstract
The intent of this study was to provide topical delivery of acetazolamide by preparing chitosan-STPP (sodium tripolyphosphate) nanoparticles of acetazolamide and evaluate the particle size, zeta potential, drug entrapment, particle morphology; in vitro drug release and in vivo efficacy. The particles showed sustained in vitro drug release which followed the Higuchi kinetic model. The results indicate that the nanoparticles released the drug by a combination of dissolution and diffusion. The optimised formulation was having particle size 188.46 ± 8.53 nm and zeta potential + 36.86 ± 0.70 mV. The particles were spherical with a polydispersity index of 0.22 ± 0.00. Powder X-ray diffraction and differential scanning calorimetry indicated diminished crystallinity of drug in the nanoparticle formulation. In the in vitro permeation study, the nanoparticle formulation showed elevated permeation as compared to that of drug solution with negative signs of corneal damage. In vitro mucoadhesion studies showed 90.34 ± 1.12% mucoadhesion. The in vivo studies involving ocular hypotensive activity in rabbits revealed significantly higher hypotensive activity (P < 0.05) as compared with plain drug solution with no signs of ocular irritation. The stability studies revealed that formulation was quite stable.
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Affiliation(s)
- Satish Manchanda
- Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar Sector III, MB Road, New Delhi 110017, India
| | - Pravat Kumar Sahoo
- Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar Sector III, MB Road, New Delhi 110017, India
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31
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Fabrication and characterization of mucoadhesive topical nanoformulations of dorzolamide HCl for ocular hypertension. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2017. [DOI: 10.1007/s40005-017-0324-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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32
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Utkin YN. Modern trends in animal venom research - omics and nanomaterials. World J Biol Chem 2017; 8:4-12. [PMID: 28289514 PMCID: PMC5329713 DOI: 10.4331/wjbc.v8.i1.4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 12/20/2016] [Accepted: 12/27/2016] [Indexed: 02/05/2023] Open
Abstract
Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and nanotechnologies in venom research are systematized concisely in this paper.
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Yu D, Li S, Wang S, Li X, Zhu M, Huang S, Sun L, Zhang Y, Liu Y, Wang S. Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats. Mar Drugs 2016; 14:md14100182. [PMID: 27727163 PMCID: PMC5082330 DOI: 10.3390/md14100182] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 08/30/2016] [Accepted: 08/31/2016] [Indexed: 12/20/2022] Open
Abstract
Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF) was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage.
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Affiliation(s)
- Daojiang Yu
- Department of Plastic Surgery, the Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
- Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
| | - Shan Li
- College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
| | - Shuai Wang
- Department of Plastic Surgery, the Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
| | - Xiujie Li
- Department of Plastic Surgery, the Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
| | - Minsheng Zhu
- Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
| | - Shai Huang
- Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
| | - Li Sun
- Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
| | - Yongsheng Zhang
- Department of Pathology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
| | - Yanli Liu
- College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
| | - Shouli Wang
- Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China.
- Institute of Radiology & Oncology, Soochow University, Suzhou 215006, China.
- Suzhou Key Laboratory of Tumor Microenvironment Pathology, Suzhou 215123, China.
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34
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Vinodhini PA, Sudha PN. Removal of heavy metal chromium from tannery effluent using ultrafiltration membrane. ACTA ACUST UNITED AC 2016. [DOI: 10.1186/s40689-016-0016-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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35
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Gamboa A, Araujo V, Caro N, Gotteland M, Abugoch L, Tapia C. Spray Freeze-Drying as an Alternative to the Ionic Gelation Method to Produce Chitosan and Alginate Nano-Particles Targeted to the Colon. J Pharm Sci 2015; 104:4373-4385. [PMID: 26305273 DOI: 10.1002/jps.24617] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 06/26/2015] [Accepted: 08/04/2015] [Indexed: 11/11/2022]
Abstract
Chitosan and alginate nano-composite (NP) carriers intended for colonic delivery containing prednisolone and inulin were obtained by two processes. Spray freeze-drying using chitosan (SFDC) or alginate (SFDA) was proposed as an alternative to the traditional chitosan-tripolyphosphate platform (CTPP). NPs were fully characterised and assessed for their yield of particles; level of prednisolone and inulin release in phosphate and Krebs buffers; and sensitivity to degradation by lysozyme, bacteria and faecal slurry. NPs based on chitosan showed similar properties (size, structure, viscoelastic behaviour), but those based on SFDC showed a higher mean release of both active ingredients, with similar efficiency of encapsulation and loading capacity for prednisolone but lower for inulin. SFDC was less degraded in the presence of lysozyme and E. coli and was degraded by B. thetaiotaomicron but not by faecal slurry. The results obtained with SFDA were promising because this NP showed good encapsulation parameters for both active ingredients and biological degradability by E. coli and faecal slurry. However, it will be necessary to use alginate derivatives to reduce its solubility and improve its mechanical behaviour.
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Affiliation(s)
- Alexander Gamboa
- Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Independencia, Santiago de Chile, Chile
| | - Valeria Araujo
- Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Independencia, Santiago de Chile, Chile
| | - Nelson Caro
- Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Independencia, Santiago de Chile, Chile
| | - Martin Gotteland
- Departamento de Nutrición, Facultad de Medicina, Universidad de Chile, Santiago de Chile, Chile
| | - Lilian Abugoch
- Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Independencia, Santiago de Chile, Chile
| | - Cristian Tapia
- Departamento de Ciencia de los Alimentos y Tecnología Química, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Independencia, Santiago de Chile, Chile.
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Diop M, Auberval N, Viciglio A, Langlois A, Bietiger W, Mura C, Peronet C, Bekel A, Julien David D, Zhao M, Pinget M, Jeandidier N, Vauthier C, Marchioni E, Frere Y, Sigrist S. Design, characterisation, and bioefficiency of insulin–chitosan nanoparticles after stabilisation by freeze-drying or cross-linking. Int J Pharm 2015; 491:402-8. [DOI: 10.1016/j.ijpharm.2015.05.065] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Revised: 05/19/2015] [Accepted: 05/25/2015] [Indexed: 12/25/2022]
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Zhang X, Wu Y, Sun K, Tan J. Effect of erythropoietin loading chitosan-tripolyphosphate nanoparticles on an IgA nephropathy rat model. Exp Ther Med 2014; 7:1659-1662. [PMID: 24926362 PMCID: PMC4043601 DOI: 10.3892/etm.2014.1643] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/21/2014] [Indexed: 12/31/2022] Open
Abstract
The aim of the present study was to investigate the effect of erythropoietin (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine (Cr) levels were measured in each group using a Biochemical Analyzer (Hitachi, Tokyo, Japan). The average size of nanoparticles was 485±12 nm and the encapsulation efficiency of EPO was 78.45%. The EPO release curve in CS-TPP-EPO nanoparticles exhibited a biphasic distribution in vitro. The levels of BUN and Cr in the CS-TPP-EPO group were significantly lower compared with the control group (P<0.05); however, the level of Hb in the CS-TPP-EPO group was higher compared with the other groups (P<0.05). The changes in Hb, BUN and Cr in the CS-TPP-EPO group were maintained for less than one week following the end of the treatment with CS-TPP-EPO nanoparticles. In conclusion, the CS-TPP-EPO nanoparticles had a lower toxicity compared with EPO and CS-TPP treatment. Furthermore, CS-TPP-EPO may improve the therapeutic effect in the IgAN model. This suggests that CS-TPP-EPO nanoparticles may be a potential therapeutic drug for the treatment of patients with IgAN.
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Affiliation(s)
- Xiaoli Zhang
- Department of Rheumatism and Nephropathy, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
| | - Yin Wu
- Department of Rheumatism and Nephropathy, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
| | - Kun Sun
- Department of Rheumatism and Nephropathy, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
| | - Jing Tan
- Department of Rheumatism and Nephropathy, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
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Vimal S, Abdul Majeed S, Taju G, Nambi K, Sundar Raj N, Madan N, Farook M, Rajkumar T, Gopinath D, Sahul Hameed A. Chitosan tripolyphosphate (CS/TPP) nanoparticles: preparation, characterization and application for gene delivery in shrimp. Acta Trop 2013; 128:486-93. [PMID: 23906611 DOI: 10.1016/j.actatropica.2013.07.013] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 07/03/2013] [Accepted: 07/19/2013] [Indexed: 12/30/2022]
Abstract
The present study examines the use of CS/TPP nanoparticles for gene delivery in different tissues of shrimp through oral route. The viral gene of WSSV was used to construct DNA vaccines using pcDNA 3.1, a eukaryotic expression vector and the constructs were named as pVP28. The CS/TPP nanoparticles were synthesized by ionic gelation process and these particles were characterized. The structure and morphology of the nanoparticles were studied by field emission scanning electron microscopy (FE-SEM) and FTIR (Fourier Transform Infrared Spectra). The cytotoxicity of CS/TPP nanoparticles was evaluated by MTT assay using fish cell line. The expression of gene was confirmed by Immuno-dot blot, ELISA and RT-PCR analyses. The results indicate that DNA can be easily delivered into shrimp by feeding with CS/TPP nanoparticles.
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Venkatesan C, Vimal S, Hameed ASS. Synthesis and characterization of chitosan tripolyphosphate nanoparticles and its encapsulation efficiency containing Russell's viper snake venom. J Biochem Mol Toxicol 2013; 27:406-11. [PMID: 23712553 DOI: 10.1002/jbt.21502] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 04/21/2013] [Accepted: 05/03/2013] [Indexed: 11/09/2022]
Abstract
Chitosan Tripolyphosphate (CS/TPP) nanoparticle is a biodegradable and nontoxic polysaccharide, used as a carrier for drug delivery. The morphology and particle-size measurements of the nanoparticles were studied by field emission scanning electron microscopy and Fourier Transform Infrared Spectroscopy (FTIR). This study aims to evaluate the impact of Russell's viper venom encapsulation on various factors and loading capacity, in addition to explore the physicochemical structure of nanoparticles. FTIR confirmed that tripolyphosphoric groups of TPP linked with ammonium groups of CS in the nanoparticles. Our results showed that CS can react with TPP to form stable cationic nanoparticles. The results also showed that encapsulation efficiency of venom at different concentrations of 20, 40, 60, 500, and 1000 µg/mL were achieved for CS/TPP nanoparticles at different concentrations of 1.5, 2, and 3 mg/mL. The cytotoxicity of CS/TPP nanoparticles was evaluated by MTT (-3 (4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, a tetrazole) assay.
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Affiliation(s)
- C Venkatesan
- Aquaculture Biotechnology Division, Department of Zoology, C.Abdul Hakeem College, Melvisharam 632 509, Vellore, India
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Arancibia R, Maturana C, Silva D, Tobar N, Tapia C, Salazar JC, Martínez J, Smith PC. Effects of chitosan particles in periodontal pathogens and gingival fibroblasts. J Dent Res 2013; 92:740-5. [PMID: 23788611 DOI: 10.1177/0022034513494816] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Chitosan is a naturally derived polymer with antimicrobial and anti-inflammatory properties. However, studies evaluating the role of chitosan in the control of periodontal pathogens and the responses of fibroblasts to inflammatory stimuli are lacking. In the present study, we analyzed whether chitosan particles may inhibit the growth of periodontal pathogens and modulate the inflammatory response in human gingival fibroblasts. Chitosan particles were generated through ionic gelation. They inhibited the growth of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans at 5 mg/mL. Conversely, IL-1β strongly stimulated PGE2 protein levels in gingival fibroblasts, and chitosan inhibited this response at 50 µg/mL. IL-1β-stimulated PGE2 production was dependent on the JNK pathway, and chitosan strongly inhibited this response. IL-1β stimulated NF-κB activation, another signaling pathway involved in PGE2 production. However, chitosan particles were unable to modify NF-κB signaling. The present study shows that chitosan exerts a predominantly anti-inflammatory activity by modulating PGE2 levels through the JNK pathway, which may be useful in the prevention or treatment of periodontal inflammation.
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Affiliation(s)
- R Arancibia
- Dentistry Academic Unit, Faculty of Medicine, Pontificia Universidad Católica de Chile
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Mohammadpour Dounighi N, Eskandari R, Avadi MR, Zolfagharian H, Mir Mohammad Sadeghi A, Rezayat M. Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system. J Venom Anim Toxins Incl Trop Dis 2012. [DOI: 10.1590/s1678-91992012000100006] [Citation(s) in RCA: 124] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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Meng J, Sturgis TF, Youan BBC. Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion. Eur J Pharm Sci 2011; 44:57-67. [PMID: 21704704 DOI: 10.1016/j.ejps.2011.06.007] [Citation(s) in RCA: 127] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Revised: 05/16/2011] [Accepted: 06/10/2011] [Indexed: 01/12/2023]
Abstract
The objective of this study was to engineer a model anti-HIV microbicide (tenofovir) loaded chitosan based nanoparticles (NPs). Box-Behnken design allowed to assess the influence of formulation variables on the size of NPs and drug encapsulation efficiency (EE%) that were analyzed by dynamic light scattering and UV spectroscopy, respectively. The effect of the NPs on vaginal epithelial cells and Lactobacillus crispatus viability and their mucoadhesion to porcine vaginal tissue were assessed by cytotoxicity assays and fluorimetry, respectively. In the optimal aqueous conditions, the EE% and NPs size were 5.83% and 207.97nm, respectively. With 50% (v/v) ethanol/water as alternative solvent, these two responses increased to 20% and 602 nm, respectively. Unlike small size (182nm) exhibiting burst release, drug release from medium (281 nm) and large (602 nm)-sized NPs fitted the Higuchi (r(2)=0.991) and first-order release (r(2)=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and L. crispatus for 48h. When the diameter of the NPs decreased from 900 to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% and percent mucoadhesion for larger size NPs was the highest. Overall, large-size, microbicide loaded chitosan NPs appeared to be promising nanomedicines for the prevention of HIV transmission.
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Affiliation(s)
- Jianing Meng
- Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, MO 64108, USA
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