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1
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Shao H, Liu M, Jiang H, Zhang Y. Polysaccharide-based drug delivery targeted approach for colon cancer treatment: A comprehensive review. Int J Biol Macromol 2025; 302:139177. [PMID: 39798740 DOI: 10.1016/j.ijbiomac.2024.139177] [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: 08/28/2024] [Revised: 12/10/2024] [Accepted: 12/23/2024] [Indexed: 01/15/2025]
Abstract
Colon cancer is a leading cause of cancer-related morbidity and mortality worldwide, necessitating advancements in therapeutic strategies to improve outcomes. Current treatment modalities, including surgery, chemotherapy, and radiation, are limited by systemic toxicity, low drug utilization rates, and off-target effects. Colon-targeted drug delivery systems (CDDS) offer a promising alternative by leveraging the colon's unique physiology, such as near-neutral pH and extended transit time, to achieve localized and controlled drug release. Polysaccharide-based CDDS, utilizing natural polymers like chitosan, cyclodextrin, pectin, guar gum, alginate, hyaluronic acid, dextran, chondroitin sulfate, and inulin, have emerged as innovative approaches for improving the specificity and efficacy of colon cancer treatments. These biocompatible and biodegradable polymers enable site-specific drug delivery, enhance tumor apoptosis, reduce systemic side effects, and improve patient compliance. This review evaluates recent advancements in polysaccharide-based CDDS, detailing their drug release mechanisms, therapeutic potential, and challenges in overcoming gastrointestinal transit and pH variability. Studies highlight the successful formulation of nanoparticles, microspheres, and other delivery systems, demonstrating targeted drug delivery, improved bioavailability, and enhanced cytotoxicity against colon cancer cells in-vitro and in-vivo. The review underscores the need for continued research on polysaccharide-based CDDS for colon cancer treatment, offering a path toward more effective, patient-centered oncological care.
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Affiliation(s)
- Hua Shao
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China
| | - Minghua Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China
| | - Hongfang Jiang
- Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China.
| | - Ying Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
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2
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Gong T, Liu X, Wang X, Lu Y, Wang X. Applications of polysaccharides in enzyme-triggered oral colon-specific drug delivery systems: A review. Int J Biol Macromol 2024; 275:133623. [PMID: 38969037 DOI: 10.1016/j.ijbiomac.2024.133623] [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: 01/30/2024] [Revised: 06/27/2024] [Accepted: 07/01/2024] [Indexed: 07/07/2024]
Abstract
Enzyme-triggered oral colon-specific drug delivery system (EtOCDDS1) can withstand the harsh stomach and small intestine environments, releasing encapsulated drugs selectively in the colon in response to colonic microflora, exerting local or systematic therapeutic effects. EtOCDDS boasts high colon targetability, enhanced drug bioavailability, and reduced systemic side effects. Polysaccharides are extensively used in enzyme-triggered oral colon-specific drug delivery systems, and its colon targetability has been widely confirmed, as their properties meet the demand of EtOCDDS. Polysaccharides, known for their high safety and excellent biocompatibility, feature modifiable structures. Some remain undigested in the stomach and small intestine, whether in their natural state or after modifications, and are exclusively broken down by colon-resident microbiota. Such characteristics make them ideal materials for EtOCDDS. This article reviews the design principles of EtOCDDS as well as commonly used polysaccharides and their characteristics, modifications, applications and specific mechanism for colon targeting. The article concludes by summarizing the limitations and potential of ETOCDDS to stimulate the development of innovative design approaches.
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Affiliation(s)
- Tingting Gong
- Institute of Medicinal Plant Development, Peking Union Medical College, No.151, Malianwa North Road, Haidian District, Beijing 100193, PR China
| | - Xinxin Liu
- Institute of Medicinal Plant Development, Peking Union Medical College, No.151, Malianwa North Road, Haidian District, Beijing 100193, PR China
| | - Xi Wang
- Institute of Medicinal Plant Development, Peking Union Medical College, No.151, Malianwa North Road, Haidian District, Beijing 100193, PR China
| | - Yunqian Lu
- Institute of Medicinal Plant Development, Peking Union Medical College, No.151, Malianwa North Road, Haidian District, Beijing 100193, PR China
| | - Xiangtao Wang
- Institute of Medicinal Plant Development, Peking Union Medical College, No.151, Malianwa North Road, Haidian District, Beijing 100193, PR China.
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3
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Vemula SK, Daravath B, Gummadi SB, Repka M. Formulation and Development of Flurbiprofen Colon-Specific Eudragit Coated Matrix Tablets: Use of a Novel Crude Banana Peel Powder as a Time-Dependent Polymer. AAPS PharmSciTech 2023; 24:189. [PMID: 37726501 DOI: 10.1208/s12249-023-02646-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 08/28/2023] [Indexed: 09/21/2023] Open
Abstract
The rationale for the current investigation is to study the crude banana peel (CBP) powder efficiency as a novel natural time-dependent polymer along with a pH-sensitive polymer to develop flurbiprofen colon-specific tablets. The direct compression method is utilized to prepare the flurbiprofen-CBP matrix tablets using 9 mm punches on the rotary tableting machine and subsequently coated with Eudragit® S 100 by a dip coating method. The tablets were evaluated for various tableting properties and in vitro drug release studies. From the results of dissolution studies, the F6 formulation showed negligible drug release (5.76% in 5 h) in the upper gastrointestinal tract and progressive release in the colon (99.08% in 24 h). Mean dissolution time, T10%, and T80% were found to be 13.33 h, 5.8 h, and 20.7 h, respectively, which explains the efficiency of the present combination of polymers for colon-specific drug release. From the dissolution studies results of stability studies, the similarity index was calculated and found to be 74.75. In conclusion, utilizing CBP as a natural, time-dependent polymer in conjunction with Eudragit® S 100 to develop the flurbiprofen tablets seems like a promising approach for delivering drugs specifically to the colon.
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Affiliation(s)
- Sateesh Kumar Vemula
- Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
| | - Bhaskar Daravath
- Department of Pharmaceutics, GITAM School of Pharmacy, GITAM Deemed to Be University, Rudraram, Patancheru, Sangareddy, Hyderabad, Telangana, India
| | | | - Michael Repka
- Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
- Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Mississippi, 38677, USA.
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4
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Predoi D, Balas M, Badea MA, Ciobanu SC, Buton N, Dinischiotu A. Dextran-Coated Iron Oxide Nanoparticles Loaded with 5-Fluorouracil for Drug-Delivery Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:1811. [PMID: 37368241 PMCID: PMC10300921 DOI: 10.3390/nano13121811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 05/27/2023] [Accepted: 06/04/2023] [Indexed: 06/28/2023]
Abstract
This study aims to design and test different formulations composed of dextran-coated iron oxide nanoparticles (IONPs) loaded with 5-Fluorouracil (5-FU) with varying nanoparticle:drug ratios on colorectal cancer cells. The stable suspension of IONPs s was synthesized by the adapted co-precipitation method. The stable suspension of IONPs was mixed with a solution of dextran and 5-FU solubilized in a saline solution. The final suspensions with optimized ratios of IONP:5-FU in the final suspension were 0.5:1, 1:1, and 1.5:1. The information on the morphology and size distribution of the IONPs suspension and IONP loads with 5-FU was obtained using scanning electron microscopy (SEM). The presence of 5-FU and dextran on the surface of the IONPs was highlighted by energy-dispersive X-ray spectroscopy (EDS) studies. The determination of the surface charge of the nanoparticles in the final suspensions of IONP:5-FU was achieved by measuring the zeta potential (ζ). The hydrodynamic diameter of the resulting suspensions of IONP:5-FU was determined by dynamic light scattering (DLS). A cytocompatibility analysis was performed using Caco-2 (human epithelial colorectal adenocarcinoma) cells. In this research, our goal was to find a relationship between the formulation ratio of nanoparticles and drug, and the cellular response after exposure, as a strategy to increase the efficacy of this drug-delivery system. The nanoparticle uptake and antitumor activity, including modulation of oxidative stress, apoptosis, and proliferation biomarkers, were analyzed. The present study showed that the nanoformulation with the ratio IONP:5-FU 1.5:1 had the highest anti-tumor efficiency. Moreover, decreased MCM-2 expression in Caco-2 cells exposed to dextran-coated iron oxide nanoparticles loaded with 5-FU was demonstrated for the first time.
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Affiliation(s)
- Daniela Predoi
- National Institute of Materials Physics, Atomistilor Street, No. 405A, P.O. Box MG 07, 077125 Magurele, Romania;
| | - Mihaela Balas
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (M.A.B.); (A.D.)
| | - Madalina Andreea Badea
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (M.A.B.); (A.D.)
- Research Institute of the University of Bucharest (ICUB), University of Bucharest, 90-92 Sos. Panduri, 050663 Bucharest, Romania
| | - Steluta Carmen Ciobanu
- National Institute of Materials Physics, Atomistilor Street, No. 405A, P.O. Box MG 07, 077125 Magurele, Romania;
| | - Nicolas Buton
- HORIBA Jobin Yvon S.A.S., 6-18, Rue du Canal, CEDEX, 91165 Longjumeau, France;
| | - Anca Dinischiotu
- Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania; (M.A.B.); (A.D.)
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Singh S, Singh G, Attri S, Kaur P, Rashid F, Bedi N, Haque S, Janahi EM, Arora S. Development and optimization of nanoparticles loaded with erucin, a dietary isothiocyanate isolated from Eruca sativa: Antioxidant and antiproliferative activities in ehrlich-ascites carcinoma cell line. Front Pharmacol 2023; 13:1080977. [PMID: 36761468 PMCID: PMC9905727 DOI: 10.3389/fphar.2022.1080977] [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: 10/26/2022] [Accepted: 12/20/2022] [Indexed: 01/26/2023] Open
Abstract
The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER.
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Affiliation(s)
- Sharabjit Singh
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India
| | - Gurdeep Singh
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India
| | - Shivani Attri
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India
| | - Prabhjot Kaur
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India
| | - Farhana Rashid
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India
| | - Neena Bedi
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Janzan, Saudi Arabia
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | | | - Saroj Arora
- Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, India
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Ibrahim IM. Advances in Polysaccharide-Based Oral Colon-Targeted Delivery Systems: The Journey So Far and the Road Ahead. Cureus 2023; 15:e33636. [PMID: 36788847 PMCID: PMC9912363 DOI: 10.7759/cureus.33636] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2023] [Indexed: 01/12/2023] Open
Abstract
Various colon-targeted oral delivery systems have been explored so far to treat colorectal diseases, including timed-release systems, prodrugs, pH-based polymer coatings, and microflora-triggered systems. Among them, the microbially triggered system has gained attention. Among various oral colon-targeted delivery systems discussed, the polysaccharide-based colon-targeted delivery system has been found to be quite promising as polysaccharides remain unaffected by gastric as well as upper intestine milieu and are only digested by colonic bacteria upon reaching the colon. The major bottleneck associated with this delivery is that non-suitability of this system during the diseased state due to decrease in bacterial count at that time. This causes the failure of delivery system to release the drug even at colonic site as the polysaccharide matrix/coat cannot be digested properly due to lack of bacteria. The co-administration of probiotics is reported to compensate for the bacterial loss besides facilitating site-specific release. However, this research is also limited at the preclinical level. Hence, efforts are required to make this technology scalable and clinically applicable. This article entails in detail various oral colon-targeted delivery systems prepared so far, as well as the limitations and benefits of polysaccharide-based oral colon-targeted delivery systems.
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Affiliation(s)
- Ibrahim M Ibrahim
- Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
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7
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Aldawsari HM, Naveen NR, Alhakamy NA, Goudanavar PS, Rao GK, Budha RR, Nair AB, Badr-Eldin SM. Compression-coated pulsatile chronomodulated therapeutic system: QbD assisted optimization. Drug Deliv 2022; 29:2258-2268. [PMID: 35838522 PMCID: PMC9477481 DOI: 10.1080/10717544.2022.2094500] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Pulsatile drug delivery systems have drawn attention in contemporary research for designing chronotherapeutic systems. The current work aims to design pulsatile ketorolac tromethamine tablets using compression coating for delayed delivery with a lag time suitable for the treatment of morning stiffness in arthritis. Rapidly disintegrating core tablets of ketorolac tromethamine were formulated using super-disintegrants, and the optimized formulation was compression using PEO WSR coagulant and Eudragit RLPO for delaying the release. The central composite design and response surface methodology were employed to optimize the formulation and process parameters namely PEO WSR Coagulant (X1), Eudragit RLPO (X2), and Hardness (X3). The dependent variables optimized were lag time and time required for 95% drug release. Analysis using response surface graphs and mathematical modeling of the results allowed identifying and quantifying the formulation variables active on the selected responses. A polynomial equation fitted to the data was used to predict the composition with optimum responses. Compression-coated pulsatile tablets’ optimized composition exhibited a lag time of 9 h and released 95% of the ketorolac tromethamine in 17.42 h. Validation of the mathematical model assured the reliability of QBD in formulation design. In vivo X-ray imaging and pharmacokinetic studies established a strong relationship between the coated polymers maintaining the desired lag time for delayed delivery of the active to coincide with the chronobiology for enhanced bioavailability at the right time when needed.
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Affiliation(s)
- Hibah M Aldawsari
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - N Raghavendra Naveen
- Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Karnataka, India
| | - Nabil A Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia.,Mohamed Saeed Tamer Chair for Pharmaceutical Industries, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Prakash S Goudanavar
- Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Karnataka, India
| | - Gsn Koteswara Rao
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, India
| | - Roja Rani Budha
- Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam, Tirupati, India
| | - Anroop B Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Shaimaa M Badr-Eldin
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.,Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
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8
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Corrie L, Gulati M, Awasthi A, Vishwas S, Kaur J, Khursheed R, Porwal O, Alam A, Parveen SR, Singh H, Chellappan DK, Gupta G, Kumbhar P, Disouza J, Patravale V, Adams J, Dua K, Singh SK. Harnessing the dual role of polysaccharides in treating gastrointestinal diseases: As therapeutics and polymers for drug delivery. Chem Biol Interact 2022; 368:110238. [DOI: 10.1016/j.cbi.2022.110238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/27/2022] [Accepted: 10/21/2022] [Indexed: 12/01/2022]
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9
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Janardhanam LSL, Deokar AS, Bollareddy SR, Venuganti VVK. Colon-Targeted Layer-by-Layer Self-assembled Film: Pharmacokinetic Analysis of BCS Class I and Class III Model Drugs. AAPS PharmSciTech 2022; 23:299. [DOI: 10.1208/s12249-022-02450-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/27/2022] [Indexed: 11/16/2022] Open
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10
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Carbohydrate Polymer-Based Targeted Pharmaceutical Formulations for Colorectal Cancer: Systematic Review of the Literature. POLYSACCHARIDES 2022. [DOI: 10.3390/polysaccharides3040040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Colon cancer is the third most diagnosed cancer worldwide, followed by lung and breast cancer. Conventional treatment methods are associated with numerous side effects and compliance issues. Thus, colon targeted drug delivery has gained much attention due to its evident advantages. Although many technologies have been explored, the use of pH-sensitive polymers, especially biodegradable polymers, holds exceptional promise. This review aims to collate research articles concerning recent advances in this area. A systematic search using multiple databases (Google Scholar, EMBASE, PubMed, MEDLINE and Scopus) was carried out following the preferred reported items for systematic reviews and meta-analyses (PRISMA) guidelines with an aim to explore the use of pH-sensitive carbohydrate polymers in developing colon targeted pharmaceutical formulations. Following screening and quality assessment for eligibility, 42 studies were included, exploring either single or a combination of carbohydrate polymers to develop targeted formulations for colon cancer therapy. Pectin (11) is the most widely used of these biopolymers, followed by chitosan (09), alginate (09) and guar gum (08). This systematic review has successfully gathered experimental evidence highlighting the importance of employing carbohydrate polymers in developing targeting formulations to manage colon cancer.
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11
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Ukani H, Pratyush, Kumar S, Aswal VK, Al‐Ghamdi AA, Malek NI. Cholesterol Mediated Stable Vesicles: A Nano Drug Delivery Vehicle for Anti‐cancer Drugs Curcumin and 5‐Fluorourecil. ChemistrySelect 2022. [DOI: 10.1002/slct.202201613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Hiral Ukani
- Ionic Liquids Research Laboratory Department of Chemistry Sardar Vallabhbhai National Institute of Technology Surat 395007 Gujarat India
| | - Pratyush
- Ionic Liquids Research Laboratory Department of Chemistry Sardar Vallabhbhai National Institute of Technology Surat 395007 Gujarat India
| | - Sugam Kumar
- Solid State Physics Division Bhabha Atomic Research Centre, Trombay Mumbai 400085 India
| | - Vinod K Aswal
- Solid State Physics Division Bhabha Atomic Research Centre, Trombay Mumbai 400085 India
| | - Azza A. Al‐Ghamdi
- Department of Chemistry College of Science Imam Abdul Rahman Bin Faisal University P.O. Box 1982 Dammam 31441 Saudi Arabia
- Basic & Applied Scientific Research Center (BASRC) Water Treatment Unit Imam Abdulrahman Bin Faisal University P.O. Box 1982 Dammam 31441 Saudi Arabia
| | - Naved I. Malek
- Ionic Liquids Research Laboratory Department of Chemistry Sardar Vallabhbhai National Institute of Technology Surat 395007 Gujarat India
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Jubeen F, Ijaz S, Jabeen I, Aftab U, Mehdi W, Altaf A, Alissa SA, Al-Ghulikah HA, Ezzine S, Bejaoui I, Iqbal M. Anticancer potential of novel 5-Fluorouracil co-crystals against MCF7 breast and SW480 colon cancer cell lines along with docking studies. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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13
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Zhang L, Wahlgren M, Bergenståhl B. Oil-Based Delivery Control Release System Targeted to the Later Part of the Gastrointestinal Tract-A Mechanistic Study. Pharmaceutics 2022; 14:pharmaceutics14050896. [PMID: 35631482 PMCID: PMC9144740 DOI: 10.3390/pharmaceutics14050896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/07/2022] [Accepted: 04/18/2022] [Indexed: 02/01/2023] Open
Abstract
Oil-based drug delivery systems have been studied in different aspects. The present study proposes a new application for an oil-based delivery system, focusing on controlled release until the drug reaches the later part of the small intestine. Bulk surfactants and interfacial surfactants were added into the oil formulation to provide a better mechanistic understating of the lipolysis. Validation of the modified in vitro method shows the overall conversion from medium-chain triglyceride oil (MCT oil) to free fatty acids (FFA) of 100 ± 4% in five replicates. This fully converted level and high reproducibility are fundamental for the following investigations where any retarding effect can be distinguished from the experimental errors. The results show that viscosity and thermodynamic activity have limited retardation. Furthermore, the former may change the kinetics of lipolysis, while the latter changes the equilibrium level. The gel-forming retarder (ethylcellulose) displayed a strong effect. Whereas the lipolysis was significantly retarded (>50%) when the retarders altered the interfacial composition (poloxamer 407), degradable interfacial surfactants did not have the same effect. However, surface-active, lipolysis-resistant retarders with a high CMC did not show a retarding effect.
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Bae H, Lee W, Song J, Hong T, Kim MH, Ham J, Song G, Lim W. Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer. Antioxidants (Basel) 2021; 10:antiox10091477. [PMID: 34573109 PMCID: PMC8469995 DOI: 10.3390/antiox10091477] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 12/12/2022] Open
Abstract
Colon cancer is a disease with a high prevalence rate worldwide, and for its treatment, a 5-fluorouracil (5-FU)-based chemotherapeutic strategy is generally used. However, conventional anticancer agents have some limitations, including the development of drug resistance. Therefore, there has recently been a demand for the improvement of antitumor agents using natural products with low side effects and high efficacy. Polydatin is a natural active compound extracted from an annual plant, and widely known for its anticancer effects in diverse types of cancer. However, it is still not clearly understood how polydatin ameliorates several drawbacks of standard anticancer drugs by reinforcing the chemosensitivity against 5-FU, and neither are the intrinsic mechanisms behind this process. In this study, we examined how polydatin produces anticancer effects in two types of colon cancer, called HCT116 and HT-29 cells. Polydatin has the ability to repress the progression of colon cancer, and causes a modification of distribution in the cell cycle by a flow cytometry analysis. It also induces mitochondrial dysfunctions through oxidative stress and the loss of mitochondrial membrane potential. The present study investigated the apoptosis caused by the disturbance of calcium regulation and the expression levels of related proteins through flow cytometry and immunoblotting analysis. It was revealed that polydatin suppresses the signaling pathways of the mitogen-activated protein kinase (MAPK) and PI3K/AKT. In addition, it was shown that polydatin combined with 5-FU counteracts drug resistance in 5-FU-resistant cells. Therefore, this study suggests that polydatin has the potential to be developed as an innovative medicinal drug for the treatment of colon cancer.
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Affiliation(s)
- Hyocheol Bae
- Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin 17104, Korea;
| | - Woonghee Lee
- Institute of Animal Molecular Biotechnology, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea; (W.L.); (J.H.)
| | - Jisoo Song
- Department of Food and Nutrition, College of Science and Technology, Kookmin University, Seoul 02707, Korea; (J.S.); (T.H.)
| | - Taeyeon Hong
- Department of Food and Nutrition, College of Science and Technology, Kookmin University, Seoul 02707, Korea; (J.S.); (T.H.)
| | - Myung Hyun Kim
- Department of Food and Nutrition, Sookmyung Women’s University, Seoul 04310, Korea;
| | - Jiyeon Ham
- Institute of Animal Molecular Biotechnology, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea; (W.L.); (J.H.)
| | - Gwonhwa Song
- Institute of Animal Molecular Biotechnology, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea; (W.L.); (J.H.)
- Correspondence: (G.S.); (W.L.); Tel.: +82-2-3290-3881 (G.S.); +82-2-910-4773 (W.L.)
| | - Whasun Lim
- Department of Food and Nutrition, College of Science and Technology, Kookmin University, Seoul 02707, Korea; (J.S.); (T.H.)
- Correspondence: (G.S.); (W.L.); Tel.: +82-2-3290-3881 (G.S.); +82-2-910-4773 (W.L.)
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15
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Bhattacharyya R, Chowdhury P. Hydrogels of Acryloyl guar gum-g-(acrylic acid-co-3sulfopropylacrylate) for high-performance adsorption and release of gentamicin sulphate. JOURNAL OF POLYMER RESEARCH 2021. [DOI: 10.1007/s10965-021-02633-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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16
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Koyyada A, Orsu P. Natural gum polysaccharides as efficient tissue engineering and drug delivery biopolymers. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102431] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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17
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Kaur G, Singh SK, Kumar R, Kumar B, Kumari Y, Gulati M, Pandey NK, Gowthamarajan K, Ghosh D, Clarisse A, Wadhwa S, Mehta M, Satija S, Dua K, Dureja H, Gupta S, Singh PK, Kapoor B, Chitranshi N, Kumar A, Porwal O. Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101980] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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18
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Entezar-Almahdi E, Mohammadi-Samani S, Tayebi L, Farjadian F. Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer. Int J Nanomedicine 2020; 15:5445-5458. [PMID: 32801699 PMCID: PMC7398750 DOI: 10.2147/ijn.s257700] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 06/29/2020] [Indexed: 12/31/2022] Open
Abstract
5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades. It is considered a first line antineoplastic agent for the treatment of colorectal cancer. Unfortunately, chemotherapy with 5-FU has several limitations, including its short half-life, high cytotoxicity and low bioavailability. In order to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency, many scientific groups have focused on designing a new delivery system to successfully deliver 5-FU to tumor sites. We provide a comprehensive review on different strategies to design effective delivery systems, including nanoformulations, drug-conjugate formulations and other strategies for the delivery of 5-FU to colorectal cancer. Furthermore, co-delivery of 5-FU with other therapeutics is discussed. This review critically highlights the recent innovations in and literature on various types of carrier system for 5-FU.
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Affiliation(s)
- Elaheh Entezar-Almahdi
- Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soliman Mohammadi-Samani
- Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.,Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Lobat Tayebi
- Marquette University, School of Dentistry, Milwaukee, WI, USA
| | - Fatemeh Farjadian
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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19
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Janardhanam LSL, Indukuri VV, Verma P, Dusane AC, Venuganti VVK. Functionalized layer-by-layer assembled film with directional 5-fluorouracil release to target colon cancer. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 115:111118. [PMID: 32600718 DOI: 10.1016/j.msec.2020.111118] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 05/06/2020] [Accepted: 05/23/2020] [Indexed: 02/09/2023]
Abstract
The objective of this work was to prepare and characterize pH-sensitive capsule containing functionalized layer-by-layer (LbL) assembled polymeric film with directional drug release and evaluate its effectiveness against colon cancer. 5-Fluorouracil (5FU) loaded LbL film was prepared by sequential adsorption of chitosan and alginate polyelectrolytes. This LbL film was coated with polycaprolactone (PCL, 95% w/w) as a backing layer to restrict 5FU release on one-side. The other side constituted the folic acid conjugated chitosan layer for cancer targeting. This film was encapsulated into a gelatin capsule coated with pH-sensitive Eudragit S100. 5FU loaded LbL film was characterized for physical and mechanical properties. Mucoadhesion studies performed using excised rabbit colon showed that chitosan-side of LbL film adhered with significantly (p < 0.05) greater strength compared with PCL-side. Non-everted rat colon-sac model and open colon membrane model studies showed greater permeation of 5FU across the colon wall when adhered to chitosan-side of LbL film compared with PCL-side of the film. Cell monolayer and 3D-spheroid model studies using Caco-2 and COLO 320DM colorectal cancer cells showed significant (p < 0.05) growth inhibition by 5FU loaded LbL film compared with free 5FU solution. In conclusion, pH-sensitive capsule containing 5FU loaded LbL film can be developed to target colorectal cancer for regional drug delivery.
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Affiliation(s)
- Leela Sai Lokesh Janardhanam
- Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India
| | - Vikram Varma Indukuri
- Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India
| | - Pratishtha Verma
- Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India
| | - Apurva Chandrashekhar Dusane
- Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana State, India
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20
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Shafiee A. Design and Fabrication of Three-Dimensional Printed Scaffolds for Cancer Precision Medicine. Tissue Eng Part A 2020; 26:305-317. [PMID: 31992154 DOI: 10.1089/ten.tea.2019.0278] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Three-dimensional (3D)-engineered scaffolds have been widely investigated as drug delivery systems (DDS) or cancer models with the aim to develop effective cancer therapies. The in vitro and in vivo models developed via 3D printing (3DP) and tissue engineering concepts have significantly contributed to our understanding of cell-cell and cell-extracellular matrix interactions in the cancer microenvironment. Moreover, 3D tumor models were used to study the therapeutic efficiency of anticancer drugs. The present study aims to provide an overview of applying the 3DP and tissue engineering concepts for cancer studies with suggestions for future research directions. The 3DP technologies being used for the fabrication of personalized DDS have been highlighted and the potential technical approaches and challenges associated with the fused deposition modeling, the inkjet-powder bed, and stereolithography as the most promising 3DP techniques for drug delivery purposes are briefly described. Then, the advances, challenges, and future perspectives in tissue-engineered cancer models for precision medicine are discussed. Overall, future advances in this arena depend on the continuous integration of knowledge from cancer biology, biofabrication techniques, multiomics and patient data, and medical needs to develop effective treatments ultimately leading to improved clinical outcomes. Impact statement Three-dimensional printing (3DP) enables the fabrication of personalized medicines and drug delivery systems. The convergence of 3DP, tissue engineering concepts, and cancer biology could significantly improve our understanding of cancer biology and contribute to the development of new cancer therapies.
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Affiliation(s)
- Abbas Shafiee
- UQ Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, Australia.,Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia.,Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service, Brisbane, Australia
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21
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Iravani S. Plant gums for sustainable and eco-friendly synthesis of nanoparticles: recent advances. INORG NANO-MET CHEM 2020. [DOI: 10.1080/24701556.2020.1719155] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Affiliation(s)
- Siavash Iravani
- Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
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22
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Patra P, Seesala VS, Soni SR, Roy RK, Dhara S, Ghosh A, Patra N, Pal S. Biopolymeric pH-responsive fluorescent gel for in-vitro and in-vivo colon specific delivery of metronidazole and ciprofloxacin. Eur Polym J 2019. [DOI: 10.1016/j.eurpolymj.2019.02.037] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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23
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Handali S, Moghimipour E, Kouchak M, Ramezani Z, Amini M, Angali KA, Saremy S, Dorkoosh FA, Rezaei M. New folate receptor targeted nano liposomes for delivery of 5-fluorouracil to cancer cells: Strong implication for enhanced potency and safety. Life Sci 2019; 227:39-50. [PMID: 31002921 DOI: 10.1016/j.lfs.2019.04.030] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 04/08/2019] [Accepted: 04/14/2019] [Indexed: 11/25/2022]
Abstract
We previously showed that folate liposomes of 5FU made from Dipalmitoylphosphatidylcholine (DPPC) induced cell death in HT-29 and HeLa cells more potently than bulk 5FU. Also, a primary 5FU liposomal formulation with phosphatidyl choline (PC) exhibited higher cytotoxicity in murine colon cancer cells. In the present study, optimization of 5FU PC liposome, mechanism of cell death induction in human cancer cell lines and its safety along with other assays have been employed for targeted PC liposomes of 5FU. Liposomes were prepared using thin layer method and optimization of preparation was assessed using central composite design (CCD) of response surface methodology (RSM). Folic acid (FA) was employed as the targeting ligand. Morphology of 5FU loaded liposomes and changes in their thermal behavior were assessed by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC), respectively. In vitro cytotoxicity was explored using MTT assay in HT-29, Caco-2, HeLa and MCF-7 cell lines. Cytotoxicity mechanism of the targeted delivery system was searched through the evaluation of reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (∆Ψm), the release of cytochrome c, the activity of caspase 3/7 and apoptosis and necrosis rate. Liposomes were spherical in shape and 5FU was successfully encapsulated into liposomes rather in an amorphous state. Our interesting results showed that in HT-29 cells targeted liposomes triggered the mitochondrial apoptotic pathway by decreasing the mitochondrial membrane potential, releasing of cytochrome c and promoting the substantial activity of caspase 3/7. In HeLa cells, however, targeted liposomes particularly activated necrosis pathway through the overproduction of ROS. Folate-liposomal 5FU showed significantly higher antitumor efficiency compared to free drug. The results of this study offer new prospects for cancer therapy with reducing systemic drug exposure and associated toxicities.
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Affiliation(s)
- Somayeh Handali
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Eskandar Moghimipour
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Kouchak
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Zahra Ramezani
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohsen Amini
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Kambiz Ahmadi Angali
- Department of Biostatistics, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sadegh Saremy
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farid Abedin Dorkoosh
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Rezaei
- Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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24
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Co-delivery of 5-fluorouracil and oxaliplatin in novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate acid)/poly(lactic-co-glycolic acid) nanoparticles for colon cancer therapy. Int J Biol Macromol 2019; 124:1299-1311. [DOI: 10.1016/j.ijbiomac.2018.09.119] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 09/12/2018] [Accepted: 09/20/2018] [Indexed: 12/11/2022]
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25
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Handali S, Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, Saremy S, Dorkoosh FA. A novel 5-Fluorouracil targeted delivery to colon cancer using folic acid conjugated liposomes. Biomed Pharmacother 2018; 108:1259-1273. [DOI: 10.1016/j.biopha.2018.09.128] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 09/22/2018] [Accepted: 09/24/2018] [Indexed: 02/07/2023] Open
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26
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Moghimipour E, Rezaei M, Kouchak M, Ramezani Z, Amini M, Ahmadi Angali K, Saremy S, Abedin Dorkoosh F, Handali S. A mechanistic study of the effect of transferrin conjugation on cytotoxicity of targeted liposomes. J Microencapsul 2018; 35:548-558. [PMID: 30445885 DOI: 10.1080/02652048.2018.1547325] [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] [Indexed: 12/30/2022]
Abstract
This study was performed to prepare 5-fluorouracil (5FU) containing targeted liposomes for the safety and efficacy enhancement. Liposomes were prepared using thin layer method and transferrin (Tf) was employed as the targeting ligand. Morphology of 5FU-loaded liposomes was assessed by transmission electron microscopy (TEM). The in vitro cytotoxicity was investigated via MTT assay on HT-29, CT26 and fibroblast cells. Mitochondrial membrane and cell death evaluations were also investigated. Resulted showed that the encapsulation efficiency (EE%) and particle size of the liposomes were 40.12% and 130 nm, respectively. TEM image implied that liposomes were spherical in shape. In cancer cells, targeted liposomes triggered the mitochondrial apoptotic pathway by lower production of reactive oxygen species (ROS) (63.58 vs 84.95 fluorescence intensity), reduced mitochondrial membrane potential and releasing of cytochrome c (68.66 vs 51.13 ng/mL). The results of this study indicated that Tf-targeted 5FU liposomes can be employed as promising nanocarrier for the delivery of drugs to cancer cells.
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Affiliation(s)
- Eskandar Moghimipour
- a Nanotechnology Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran.,b Cellular and Molecular Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Mohsen Rezaei
- c Department of Toxicology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
| | - Maryam Kouchak
- a Nanotechnology Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Zahra Ramezani
- a Nanotechnology Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Mohsen Amini
- d Department of Medicinal Chemistry, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran
| | - Kambiz Ahmadi Angali
- e Department of Biostatistics, School of Public Health , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Sadegh Saremy
- b Cellular and Molecular Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Farid Abedin Dorkoosh
- f Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.,g Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences , Tehran , Iran
| | - Somayeh Handali
- a Nanotechnology Research Center , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
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27
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Gioumouxouzis CI, Chatzitaki AT, Karavasili C, Katsamenis OL, Tzetzis D, Mystiridou E, Bouropoulos N, Fatouros DG. Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms. AAPS PharmSciTech 2018; 19:3362-3375. [PMID: 29948989 DOI: 10.1208/s12249-018-1084-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 05/24/2018] [Indexed: 11/30/2022] Open
Abstract
Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.
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28
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Sharma N, Sharma A, Nishad DK, Khanna K, Sharma BG, Kakkar D, Bhatnagar A. Development and Gamma Scintigraphy Study of Trigonella foenum-graecum (Fenugreek) Polysaccharide-Based Colon Tablet. AAPS PharmSciTech 2018; 19:2564-2571. [PMID: 29948987 DOI: 10.1208/s12249-018-1066-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 05/01/2018] [Indexed: 11/30/2022] Open
Abstract
The major concern with the use of some synthetic excipients is their safety towards biological tissues, hence influencing the reliability of products. With the aim to minimize dependency on highly toxic synthetic excipients, the present study was designed to deliver metronidazole (MNZ) into the colonic region for localized treatment of amoebiasis using natural polysaccharide-based drug delivery. Compression-coated tablets were prepared using water extractable natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties of the tablets were evaluated and dissolution study was performed at pH 1.2, 6.8, and 7.4 with rat cecal material. Results indicate that all batches demonstrated pH-dependent drug release and prevented release into the stomach, allowing traces into the intestine and highest availability into the colon. A significant correlation (r2 = 0.975) was found between the coating levels of extracted polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo study conducted on human volunteers showed a small intestinal transit time, i.e., 3-5 (4.2 ± 0.4) h and confirmed that the tablets reached the colon within 6-8 h. The present study revealed that the FG polysaccharide-based double compression tablets may be promising colon-specific drug carriers with reduced toxic effects of commonly used synthetic excipients.
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Colon targeted beads loaded with pterostilbene: Formulation, optimization, characterization and in vivo evaluation. Saudi Pharm J 2018; 27:71-81. [PMID: 30662309 PMCID: PMC6323150 DOI: 10.1016/j.jsps.2018.07.021] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Accepted: 07/19/2018] [Indexed: 11/20/2022] Open
Abstract
Background Pterostilbene has a proven chemopreventive effect for colon carcinogenesis but suffers low bioavailability limitations and therefore unable to reach the colonic tissue. Objective and methodology To overcome the issue of low bioavailability, pterostilbene was formulated into an oral colon targeted beads by ionic gelation method using pectin and zinc acetate. Optimization was carried out by 23 factorial design whereby the effect of pectin concentration (X1), zinc acetate concentration (X2) and pterostilbene:pectin ratio (X3) were studied on entrapment efficiency (Y1) and in vitro drug release till 24 h (Y2). The optimized beads were characterized for shape and size, swelling and surface morphology. The optimized beads were uniformly coated with Eudragit S-100 using fluidized bed coater. Optimized coated beads were characterized for in vitro drug release till 24 h and surface morphology. Pharmacokinetic and organ distribution study were performed in rats to ascertain the release of pterostilbene in colon. Results The optimized formulation comprised of 2% w/v of pectin concentration (X1), 2% w/v of zinc acetate concentration (X2) and 1:4 of pterostilbene:pectin ratio (X3), which showed a satisfactory entrapment efficiency (64.80%) and in vitro release (37.88%) till 24 h. The zinc pectinate beads exhibited sphericity, uniform size distribution, adequate swelling and rough surface. The optimized coated beads achieved 15% weight gain, displayed smooth surface and optimum drug release. Pterostilbene from optimized coated beads appeared in the plasma at 14 h and reached the Cmax at 22 h (Tmax), whereas plain pterostilbene exhibited Tmax of 3 h. Discussion and conclusion Thus, larger distribution of pterostilbene was obtained in the colonic tissue compared to stomach and small intestinal tissues. Thus, delayed Tmax and larger distribution of pterostilbene in colonic tissue confirmed the targeting of beads to colon.
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Al-Lawati H, Aliabadi HM, Makhmalzadeh BS, Lavasanifar A. Nanomedicine for immunosuppressive therapy: achievements in pre-clinical and clinical research. Expert Opin Drug Deliv 2018; 15:397-418. [DOI: 10.1080/17425247.2018.1420053] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Hanan Al-Lawati
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
| | | | | | - Afsaneh Lavasanifar
- Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
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31
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Transferrin targeted liposomal 5-fluorouracil induced apoptosis via mitochondria signaling pathway in cancer cells. Life Sci 2017; 194:104-110. [PMID: 29275107 DOI: 10.1016/j.lfs.2017.12.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 12/16/2017] [Accepted: 12/20/2017] [Indexed: 01/17/2023]
Abstract
The purpose of this study was to prepare transferrin (Tf) targeted liposomal 5-Fluorouracil (5FU) to improve the safety and efficacy of the drug. Liposomes were prepared using thin layer method. Morphology of liposomes was characterized by transmission electron microscopy (TEM) and their particle size was also determined. The in vitro cytotoxicity was investigated via MTT assay on HT-29 (as cancer cell) and fibroblast (as normal cell). Moreover, cytotoxicity mechanism of targeted liposomes was determined through the production of reactive oxygen species (ROS), mitochondrial membrane potential (∆Ψm) and release of cytochrome c. Results showed that encapsulation efficiency (EE%) was 58.66±0.58 and average size of liposomes was 107nm. Also, nano-particles were spherical as shown by TEM. MTT assay on HT-29 cells revealed the higher cytotoxic activity of targeted liposomes in comparison to free drug and non-targeted liposome. In contrast, comparing with cancer cells, targeted liposomes had no cytotoxic effect on normal cells. In addition, targeted liposomes induced apoptosis through activation of mitochondrial apoptosis pathways, as evidenced by decreased mitochondrial membrane potential and release of cytochrome c. Results of the study indicated that targeted liposomes would provide a potential strategy to treat colon cancer by inducing apoptosis via mitochondria signaling pathway with reducing dose of the drug and resulting fewer side-effects.
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32
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Park HJ, Jung HJ, Ho MJ, Lee DR, Cho HR, Choi YS, Jun J, Son M, Kang MJ. Colon-targeted delivery of solubilized bisacodyl by doubly enteric-coated multiple-unit tablet. Eur J Pharm Sci 2017; 102:172-179. [DOI: 10.1016/j.ejps.2017.03.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/07/2017] [Accepted: 03/05/2017] [Indexed: 11/24/2022]
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33
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Enhancement of site specific delivery of diloxanide furoate as an antiamoebic drug. Eur J Pharm Sci 2016; 86:50-7. [DOI: 10.1016/j.ejps.2016.03.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2015] [Revised: 03/03/2016] [Accepted: 03/03/2016] [Indexed: 11/23/2022]
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34
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Mundargi RC, Tan EL, Seo J, Cho NJ. Encapsulation and controlled release formulations of 5-fluorouracil from natural Lycopodium clavatum spores. J IND ENG CHEM 2016. [DOI: 10.1016/j.jiec.2016.01.022] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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35
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Vemula SK. A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets. AAPS PharmSciTech 2015; 16:1465-73. [PMID: 26017285 DOI: 10.1208/s12249-015-0340-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Accepted: 05/18/2015] [Indexed: 11/30/2022] Open
Abstract
A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.
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Vemula SK, Katkum R. Formulation, Development and Pharmacokinetics of Ketorolac Tromethamine Colon Targeted Guar Gum Compression Coated Tablets. ACTA ACUST UNITED AC 2015. [DOI: 10.1080/22297928.2015.1069755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Vemula SK, Katkum R. Colon-specific double-compression coated pulsatile tablets of ketorolac tromethamine: Formulation development and pharmacokinetics. J Drug Deliv Sci Technol 2015. [DOI: 10.1016/j.jddst.2015.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Vemula SK. Formulation and pharmacokinetics of colon-specific double-compression coated mini-tablets: Chronopharmaceutical delivery of ketorolac tromethamine. Int J Pharm 2015; 491:35-41. [DOI: 10.1016/j.ijpharm.2015.06.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 06/02/2015] [Accepted: 06/05/2015] [Indexed: 10/23/2022]
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Palugan L, Cerea M, Zema L, Gazzaniga A, Maroni A. Coated pellets for oral colon delivery. J Drug Deliv Sci Technol 2015. [DOI: 10.1016/j.jddst.2014.12.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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40
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41
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Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review. Prog Polym Sci 2014. [DOI: 10.1016/j.progpolymsci.2014.07.010] [Citation(s) in RCA: 333] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Vemula SK, Veerareddy PR, Devadasu VR. Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets. Eur J Drug Metab Pharmacokinet 2014; 40:301-11. [PMID: 24916715 DOI: 10.1007/s13318-014-0210-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Accepted: 05/31/2014] [Indexed: 11/26/2022]
Abstract
Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.
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Affiliation(s)
- Sateesh Kumar Vemula
- Department of Pharmaceutics, Chaitanya College of Pharmacy Education and Research, Kishanpura, Hanamkonda, Warangal, 506001, Andhra Pradesh, India,
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Pharmacokinetics of ketorolac tromethamine compression-coated tablets for colon delivery. Drug Deliv Transl Res 2014; 4:310-9. [DOI: 10.1007/s13346-014-0195-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Aminabhavi TM, Nadagouda MN, Joshi SD, More UA. Guar gum as platform for the oral controlled release of therapeutics. Expert Opin Drug Deliv 2014; 11:753-66. [DOI: 10.1517/17425247.2014.897326] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Colon targeted guar gum compression coated tablets of flurbiprofen: formulation, development, and pharmacokinetics. BIOMED RESEARCH INTERNATIONAL 2013; 2013:287919. [PMID: 24260738 PMCID: PMC3821905 DOI: 10.1155/2013/287919] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 08/28/2013] [Accepted: 09/18/2013] [Indexed: 11/18/2022]
Abstract
The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The Cmax of colon targeted tablets was 11956.15 ng/mL at Tmax of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen.
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Overcoming therapeutic obstacles in inflammatory bowel diseases: A comprehensive review on novel drug delivery strategies. Eur J Pharm Sci 2013; 49:712-22. [DOI: 10.1016/j.ejps.2013.04.031] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2013] [Revised: 04/14/2013] [Accepted: 04/29/2013] [Indexed: 02/07/2023]
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Maiti S, Chowdhury M, Datta R, Ray S, Sa B. Novel gastroulcer protective micro(hydro)gels of sulfated locust bean gum-aluminium complex for immediate release of diclofenac sodium. J Drug Target 2013; 21:265-276. [DOI: 10.3109/1061186x.2012.745548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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49
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Ramasamy T, Ruttala HB, Shanmugam S, Umadevi SK. Eudragit-coated aceclofenac-loaded pectin microspheres in chronopharmacological treatment of rheumatoid arthritis. Drug Deliv 2013; 20:65-77. [DOI: 10.3109/10717544.2012.762434] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Elyagoby A, Layas N, Wong TW. Colon-specific delivery of 5-fluorouracil from zinc pectinate pellets through in situ intracapsular ethylcellulose-pectin plug formation. J Pharm Sci 2012; 102:604-16. [PMID: 23225084 DOI: 10.1002/jps.23388] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Revised: 10/02/2012] [Accepted: 10/26/2012] [Indexed: 02/06/2023]
Abstract
Conventional fluid-bed and immersion film coating of hydrophilic zinc pectinate pellets by hydrophobic ethylcellulose is met with fast drug release. This study explored in situ intracapsular pellet coating for colon-specific delivery of 5-fluorouracil (5-FU). The solid coating powder constituted ethylcellulose and pectin in weight ratios of 11:0 to 2:9. Its weight ratio to pellets varied between 2:3 and 3:2. Pectin was used as excipient of core pellets and coating powder in view of its potential use in colon cancer treatment. Delayed 5-FU release and core pectin dissolution were attainable when the weight ratio of solid coating powder to pellets was kept at 3:2, and weight ratio of ethylcellulose and pectin in coating powder was kept at 8:3 with particle size of ethylcellulose reduced to 22 μm. In situ intracapsular wetting of pectin coat by dissolution medium resulted in the formation of ethylcellulose plug interconnecting with pellets through the binding action of pectin. Less than 25% of drug was released at the upper gastrointestinal tract. The majority of drug was released upon prolonged dissolution and in response to colonic enzyme pectinase, which digested core pellets.
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Affiliation(s)
- A Elyagoby
- Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor 42300, Malaysia
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