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Dahri M, Beheshtizadeh N, Seyedpour N, Nakhostin-Ansari A, Aghajani F, Seyedpour S, Masjedi M, Farjadian F, Maleki R, Adibkia K. Biomaterial-based delivery platforms for transdermal immunotherapy. Biomed Pharmacother 2023; 165:115048. [PMID: 37385212 DOI: 10.1016/j.biopha.2023.115048] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/14/2023] [Accepted: 06/20/2023] [Indexed: 07/01/2023] Open
Abstract
Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.
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Affiliation(s)
- Mohammad Dahri
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Computational Biology and Chemistry Group (CBCG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nima Beheshtizadeh
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Regenerative Medicine group (REMED), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Nasrin Seyedpour
- Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran
| | - Amin Nakhostin-Ansari
- Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Aghajani
- Research Development Center, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Simin Seyedpour
- Nanomedicine Research Association (NRA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Moein Masjedi
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Farjadian
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Maleki
- Department of Chemical Technologies, Iranian Research Organization for Sciences and Technology (IROST), P.O. Box 33535111 Tehran, Iran.
| | - Khosro Adibkia
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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2
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Kang H, Zuo Z, Lin R, Yao M, Han Y, Han J. The most promising microneedle device: present and future of hyaluronic acid microneedle patch. Drug Deliv 2022; 29:3087-3110. [PMID: 36151726 PMCID: PMC9518289 DOI: 10.1080/10717544.2022.2125600] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 09/06/2022] [Accepted: 09/12/2022] [Indexed: 11/26/2022] Open
Abstract
Microneedle patch (MNP) is an alternative to the oral route and subcutaneous injection with unique advantages such as painless administration, good compliance, and fewer side effects. Herein, we report MNP as a prominent strategy for drug delivery to treat local or systemic disease. Hyaluronic acid (HA) has advantageous properties, such as human autologous source, strong water absorption, biocompatibility, and viscoelasticity. Therefore, the Hyaluronic acid microneedle patch (HA MNP) occupies a large part of the MNP market. HA MNP is beneficial for wound healing, targeted therapy of certain specific diseases, extraction of interstitial skin fluid (ISF), and preservation of drugs. In this review, we summarize the benefits of HA and cross-linked HA (x-HA) as an MNP matrix. Then, we introduce the types of HA MNP, delivered substances, and drug distribution. Finally, we focus on the biomedical application of HA MNP as an excellent drug carrier in some specific diseases and the extraction and analysis of biomarkers. We also discuss the future development prospect of HA MNP in transdermal drug delivery systems (TDDS).
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Affiliation(s)
- Huizhi Kang
- Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China
| | - Zhuo Zuo
- Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China
| | - Ru Lin
- Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China
| | - Muzi Yao
- Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China
| | - Yang Han
- School of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
| | - Jing Han
- Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China
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3
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Liu S, Yang G, Li M, Sun F, Li Y, Wang X, Gao Y, Yang P. Transcutaneous immunization via dissolving microneedles protects mice from lethal influenza H7N9 virus challenge. Vaccine 2022; 40:6767-6775. [PMID: 36243592 DOI: 10.1016/j.vaccine.2022.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 08/16/2022] [Accepted: 09/02/2022] [Indexed: 11/06/2022]
Abstract
Avian influenza H7N9 virus has first emerged in 2013 and since then has spread in China in five seasonal waves. In humans, influenza H7N9 virus infection is associated with a high fatality rate; thus, an effective vaccine for this virus is needed. In the present study, we evaluated the usefulness of dissolving microneedles (MNs) loaded with influenza H7N9 vaccine in terms of the dissolution time, insertion capacity, insertion depth, and structural integrity of H7N9 virus in vitro. Our in vitro results showed MNs dissolved within 6 mins. The depth of skin penetration was 270 µm. After coating with a matrix material solution, the H7N9 proteins were agglomerated. We detected the H7N9 delivery time and humoral immune response in vivo. In a mouse model, the antigen retention time was longer for MNs than for intramuscular (IM) injection. The humoral response showed that similar to IM administration, MN administration increased the levels of functional and systematic antibodies and protection against the live influenza A/Anhui/01/2013 virus (Ah01/H7N9). The protection level was determined by the analysis of pathological sections of infected lungs. MN and IM administration yielded results superior to those in the control group. Taken together, these findings demonstrate that the use of dissolving MNs to deliver influenza H7N9 vaccines is a promising immunization approach.
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Affiliation(s)
- Siqi Liu
- The First Medical Center of Chinese PLA General Hospital, Beijing 100835, China; Department of Rheumatology and Clinical Immunology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, NL, the Netherlands
| | - Guozhong Yang
- Key Laboratory of Photo Chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China
| | - Minghui Li
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
| | - Fang Sun
- The First Medical Center of Chinese PLA General Hospital, Beijing 100835, China
| | - Yufeng Li
- The First Medical Center of Chinese PLA General Hospital, Beijing 100835, China
| | - Xiliang Wang
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
| | - Yunhua Gao
- Key Laboratory of Photo Chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.
| | - Penghui Yang
- The First Medical Center of Chinese PLA General Hospital, Beijing 100835, China.
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4
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Ali M, Namjoshi S, Benson HAE, Mohammed Y, Kumeria T. Dissolvable polymer microneedles for drug delivery and diagnostics. J Control Release 2022; 347:561-589. [PMID: 35525331 DOI: 10.1016/j.jconrel.2022.04.043] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 10/18/2022]
Abstract
Dissolvable transdermal microneedles (μND) are promising micro-devices used to transport a wide selection of active compounds into the skin. To provide an effective therapeutic outcome, μNDs must pierce the human stratum corneum (~10 to 20 μm), without rupturing or bending during penetration, then release their cargo at the predetermined area and time. The ability of dissolvable μND arrays/patches to sufficiently pierce the skin is a crucial requirement, which depends on the material composition, μND geometry and fabrication techniques. This comprehensive review not only provides contemporary knowledge on the μND design approaches, but also the materials science facilitating these delivery systems and the opportunities these advanced materials can provide to enhance clinical outcomes.
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Affiliation(s)
- Masood Ali
- Therapeutics Research Group, The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD 4102, Australia
| | - Sarika Namjoshi
- Therapeutics Research Group, The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD 4102, Australia; Vaxxas Pty Ltd, Brisbane, Woolloongabba, QLD 4102, Australia
| | - Heather A E Benson
- Curtin Medical School, Curtin University, Bentley, WA 6102, Australia; UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia; Basil Hetzel institute for Translational Health Research, Adelaide, SA 5001, Australia.
| | - Yousuf Mohammed
- Therapeutics Research Group, The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Brisbane, QLD 4102, Australia.
| | - Tushar Kumeria
- School of Materials Science and Engineering, The University of New South Wales, Sydney. NSW 2052, Australia; Australian Centre for Nanomedicine, The University of New South Wales, Sydney, NSW 2052, Australia; School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia.
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Hassan J, Haigh C, Ahmed T, Uddin MJ, Das DB. Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges. Pharmaceutics 2022; 14:1066. [PMID: 35631652 PMCID: PMC9144974 DOI: 10.3390/pharmaceutics14051066] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/27/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
To prevent the coronavirus disease 2019 (COVID-19) pandemic and aid restoration to prepandemic normality, global mass vaccination is urgently needed. Inducing herd immunity through mass vaccination has proven to be a highly effective strategy for preventing the spread of many infectious diseases, which protects the most vulnerable population groups that are unable to develop immunity, such as people with immunodeficiencies or weakened immune systems due to underlying medical or debilitating conditions. In achieving global outreach, the maintenance of the vaccine potency, transportation, and needle waste generation become major issues. Moreover, needle phobia and vaccine hesitancy act as hurdles to successful mass vaccination. The use of dissolvable microneedles for COVID-19 vaccination could act as a major paradigm shift in attaining the desired goal to vaccinate billions in the shortest time possible. In addressing these points, we discuss the potential of the use of dissolvable microneedles for COVID-19 vaccination based on the current literature.
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Affiliation(s)
- Jasmin Hassan
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
| | - Charlotte Haigh
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK;
| | - Tanvir Ahmed
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
| | - Md Jasim Uddin
- Drug Delivery & Therapeutics Lab, Dhaka 1212, Bangladesh; (J.H.); (T.A.)
- Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent ME4 4TB, UK
- Department of Pharmacy, Brac University, 66 Mohakhali, Dhaka 1212, Bangladesh
| | - Diganta B. Das
- Department of Chemical Engineering, Loughborough University, Epinal Way, Loughborough LE11 3TU, UK;
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Trends in Drug- and Vaccine-based Dissolvable Microneedle Materials and Methods of Fabrication. Eur J Pharm Biopharm 2022; 173:54-72. [DOI: 10.1016/j.ejpb.2022.02.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/24/2022] [Accepted: 02/19/2022] [Indexed: 12/18/2022]
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Cordeiro AS, Patil-Sen Y, Shivkumar M, Patel R, Khedr A, Elsawy MA. Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application. Pharmaceutics 2021; 13:2091. [PMID: 34959372 PMCID: PMC8707864 DOI: 10.3390/pharmaceutics13122091] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 02/07/2023] Open
Abstract
Viral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians.
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Affiliation(s)
- Ana Sara Cordeiro
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK; (A.S.C.); (M.S.); (A.K.)
| | - Yogita Patil-Sen
- Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, National Health Service, Wigan WN6 0SZ, UK;
| | - Maitreyi Shivkumar
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK; (A.S.C.); (M.S.); (A.K.)
| | - Ronak Patel
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK;
| | - Abdulwahhab Khedr
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK; (A.S.C.); (M.S.); (A.K.)
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Mohamed A. Elsawy
- Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK; (A.S.C.); (M.S.); (A.K.)
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9
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Yin M, Wu J, Deng M, Wang P, Ji G, Wang M, Zhou C, Blum NT, Zhang W, Shi H, Jia N, Wang X, Huang P. Multifunctional Magnesium Organic Framework-Based Microneedle Patch for Accelerating Diabetic Wound Healing. ACS NANO 2021; 15:17842-17853. [PMID: 34761898 DOI: 10.1021/acsnano.1c06036] [Citation(s) in RCA: 163] [Impact Index Per Article: 40.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Diabetic wound healing is one of the major challenges in the biomedical fields. The conventional single drug treatments have unsatisfactory efficacy, and the drug delivery effectiveness is restricted by the penetration depth. Herein, we develop a magnesium organic framework-based microneedle patch (denoted as MN-MOF-GO-Ag) that can realize transdermal delivery and combination therapy for diabetic wound healing. Multifunctional magnesium organic frameworks (Mg-MOFs) are mixed with poly(γ-glutamic acid) (γ-PGA) hydrogel and loaded into the tips of MN-MOF-GO-Ag, which slowly releases Mg2+ and gallic acid in the deep layer of the dermis. The released Mg2+ induces cell migration and endothelial tubulogenesis, while gallic acid, a reactive oxygen species-scavenger, promotes antioxidation. Besides, the backing layer of MN-MOF-GO-Ag is made of γ-PGA hydrogel and graphene oxide-silver nanocomposites (GO-Ag) which further enables excellent antibacterial effects for accelerating wound healing. The therapeutic effects of MN-MOF-GO-Ag on wound healing are demonstrated with the full-thickness cutaneous wounds of a diabetic mouse model. The significant improvement of wound healing is achieved for mice treated with MN-MOF-GO-Ag.
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Affiliation(s)
- Mengting Yin
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jiayingzi Wu
- Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
| | - Mingwu Deng
- Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Pei Wang
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Guangyu Ji
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Mingsong Wang
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Chaohui Zhou
- The Education Ministry Key Laboratory of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China
| | - Nicholas Thomas Blum
- Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
| | - Wenjie Zhang
- Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Huali Shi
- The Education Ministry Key Laboratory of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China
| | - Nengqin Jia
- The Education Ministry Key Laboratory of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China
| | - Xiansong Wang
- Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
- Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Peng Huang
- Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen 518060, China
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10
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Bhadale RS, Londhe VY. A systematic review of carbohydrate-based microneedles: current status and future prospects. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:89. [PMID: 34331594 PMCID: PMC8325649 DOI: 10.1007/s10856-021-06559-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 07/07/2021] [Indexed: 06/01/2023]
Abstract
Microneedles (MNs) are minimally invasive tridimensional biomedical devices that bypass the skin barrier resulting in systemic and localized pharmacological effects. Historically, biomaterials such as carbohydrates, due to their physicochemical properties, have been used widely to fabricate MNs. Owing to their broad spectrum of functional groups, carbohydrates permit designing and engineering with tunable properties and functionalities. This has led the carbohydrate-based microarrays possessing the great potential to take a futuristic step in detecting, drug delivery, and retorting to biologicals. In this review, the crucial and extensive summary of carbohydrates such as hyaluronic acid, chitin, chitosan, chondroitin sulfate, cellulose, and starch has been discussed systematically, using PRISMA guidelines. It also discusses different approaches for drug delivery and the mechanical properties of biomaterial-based MNs, till date, progress has been achieved in clinical translation of carbohydrate-based MNs, and regulatory requirements for their commercialization. In conclusion, it describes a brief perspective on the future prospects of carbohydrate-based MNs referred to as the new class of topical drug delivery systems.
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Affiliation(s)
- Rupali S Bhadale
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle [W], Mumbai, 400056, Maharashtra, India
| | - Vaishali Y Londhe
- Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle [W], Mumbai, 400056, Maharashtra, India.
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Yenkoidiok-Douti L, Barillas-Mury C, Jewell CM. Design of Dissolvable Microneedles for Delivery of a Pfs47-Based Malaria Transmission-Blocking Vaccine. ACS Biomater Sci Eng 2021; 7:1854-1862. [PMID: 33616392 PMCID: PMC8113916 DOI: 10.1021/acsbiomaterials.0c01363] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The development of effective malaria vaccines remains a global health priority. In addition to an effective vaccine, there is urgent demand for effective delivery technologies that can be easily deployed. The need for effective vaccine delivery tools is particularly pertinent in resource-poor settings where access to healthcare is limited. Microneedles are micron-scale structures that offer distinct advantages for vaccine delivery by efficiently targeting skin-resident immune cells, eliminating injection-associated pain, and improving patient compliance. Here, we developed and characterized a candidate malaria vaccine loaded and deployed using dissolvable microneedle arrays. Of note, a newly indicated human-relevant antigen was employed, Plasmodium falciparum surface protein P47. P47 and a potent toll-like receptor (TLR9) agonist vaccine adjuvant, CpG, were fabricated into microneedles using a gelatin polymer. Protein binding, ELISA, and fluorescence analysis confirmed the molecular structure, and the function of the P47 antigen and CpG was maintained after fabrication, storage, and release from microneedles. In cell culture, the cargo released from the microneedle arrays triggered TLR9 signaling and activated primary dendritic cells at levels similar to native, unincorporated vaccine components. Together, these studies demonstrate the potential of microneedles as an easily deployable strategy for a P47-based malaria vaccine.
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Affiliation(s)
- Lampouguin Yenkoidiok-Douti
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, United States
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, 20852, United States
| | - Carolina Barillas-Mury
- Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, 20852, United States
| | - Christopher M. Jewell
- Fischell Department of Bioengineering, University of Maryland, College Park, 8278 Paint Branch Drive, College Park, MD, 20742, United States
- Department of Veterans Affairs, VA Maryland Health Care System 10. N Green Street, Baltimore, MD 21201, USA
- Robert E. Fischell Institute for Biomedical Devices, 8278 Paint Branch Drive, College Park, MD 20742, United States
- Department of Microbiology and Immunology, University of Maryland Medical School, 685 West Baltimore Street, HSF-I Suite 380, Baltimore, MD, 21201, United States
- Marlene and Stewart Greenebaum Cancer Center, 22 S. Greene Street, Suite N9E17, Baltimore, MD 21201, United States
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12
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Moniz T, Costa Lima SA, Reis S. Marine polymeric microneedles for transdermal drug delivery. Carbohydr Polym 2021; 266:118098. [PMID: 34044917 DOI: 10.1016/j.carbpol.2021.118098] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 12/16/2022]
Abstract
Transdermal drug delivery is considered one of the most attractive routes for administration of pharmaceutic and cosmetic active ingredients due to the numerous advantages, especially over oral and intravenous methodologies. However, some limitations still exist mainly regarding the need to improve the drugs permeation across the skin. For this, several strategies have been described, considering the application of chemical permeation enhancers, drugs' nanoformulations and physical methods. Of these, microneedles have been proposed in the last years as promising strategies to enhance transdermal drug delivery. In this review, different types of microneedles are described, and the most commonly used methods of fabrication systematized, as well as the materials typically used and their main therapeutical applications. A special attention is paid to polymeric microneedles, particularly those made from sustainable marine polysaccharides like chitosan, alginate and hyaluronic acid. The applications of marine based polymeric microneedle devices for transdermal drug delivery are examined in detail and the perspectives of translation from the clinical trials to the market demonstrated.
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Affiliation(s)
- Tânia Moniz
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
| | - Sofia A Costa Lima
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
| | - Salette Reis
- LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
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O’Shea J, Prausnitz MR, Rouphael N. Dissolvable Microneedle Patches to Enable Increased Access to Vaccines against SARS-CoV-2 and Future Pandemic Outbreaks. Vaccines (Basel) 2021; 9:320. [PMID: 33915696 PMCID: PMC8066809 DOI: 10.3390/vaccines9040320] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 03/25/2021] [Accepted: 03/30/2021] [Indexed: 01/02/2023] Open
Abstract
Vaccines are an essential component of pandemic preparedness but can be limited due to challenges in production and logistical implementation. While vaccine candidates were rapidly developed against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), immunization campaigns remain an obstacle to achieving herd immunity. Dissolvable microneedle patches are advantageous for many possible reasons: improved immunogenicity; dose-sparing effects; expected low manufacturing cost; elimination of sharps; reduction of vaccine wastage; no need for reconstitution; simplified supply chain, with reduction of cold chain supply through increased thermostability; ease of use, reducing the need for healthcare providers; and greater acceptability compared to traditional hypodermic injections. When applied to coronavirus disease 2019 (COVID-19) and future pandemic outbreaks, microneedle patches have great potential to improve vaccination globally and save many lives.
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Affiliation(s)
- Jesse O’Shea
- Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, 500 Irvin Court, Suite 200, Decatur, Atlanta, GA 30030, USA;
| | - Mark R. Prausnitz
- School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA;
| | - Nadine Rouphael
- Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, 500 Irvin Court, Suite 200, Decatur, Atlanta, GA 30030, USA;
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14
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Abstract
The current situation, heavily influenced by the ongoing pandemic, puts vaccines back into the spotlight. However, the conventional and traditional vaccines present disadvantages, particularly related to immunogenicity, stability, and storage of the final product. Often, such products require the maintenance of a “cold chain,” impacting the costs, the availability, and the distribution of vaccines. Here, after a recall of the mode of action of vaccines and the types of vaccines currently available, we analyze the past, present, and future of vaccine formulation. The past focuses on conventional formulations, the present discusses the use of nanoparticles for vaccine delivery and as adjuvants, while the future presents microneedle patches as alternative formulation and administration route. Finally, we compare the advantages and disadvantages of injectable solutions, nanovaccines, and microneedles in terms of efficacy, stability, and patient-friendly design. Different approaches to vaccine formulation development, the conventional vaccine formulations from the past, the current development of lipid nanoparticles as vaccines, and the near future microneedles formulations are discussed in this review. ![]()
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15
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Elahpour N, Pahlevanzadeh F, Kharaziha M, Bakhsheshi-Rad HR, Ramakrishna S, Berto F. 3D printed microneedles for transdermal drug delivery: A brief review of two decades. Int J Pharm 2021; 597:120301. [PMID: 33540018 DOI: 10.1016/j.ijpharm.2021.120301] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/13/2021] [Accepted: 01/18/2021] [Indexed: 12/31/2022]
Abstract
Microneedle (MN) technology shows excellent potential in controlled drug delivery, which has got rising attention from investigators and clinics. MNs can pierce through the stratum corneum layer of the skin into the epidermis, evading interaction with nerve fibers. MN patches have been fabricated using various types of materials and application processes. Recently, three-dimensional (3D) printing gives the prototyping and manufacturing methods the flexibility to produce the MN patches in a one-step manner with high levels of shape complexity and duplicability. This review aims to go through the last successes in 3D printed MN-based patches. In this regard, after the evaluation of various types of MNs and fabrication techniques, we will study different 3D printing approaches applied for MN patch fabrication. We further highlight the state of the art of the long-acting MNs and related progress with a specific look at what should come within the scope of upcoming researches.
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Affiliation(s)
- Nafiseh Elahpour
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Farnoosh Pahlevanzadeh
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Mahshid Kharaziha
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
| | - Hamid Reza Bakhsheshi-Rad
- Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran.
| | - Seeram Ramakrishna
- Department of Mechanical Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.
| | - Filippo Berto
- Department of Mechanical and Industrial Engineering, Norwegian University of Science and Technology, 7491 Trondheim, Norway
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16
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Wallis M, Al-Dulimi Z, Tan DK, Maniruzzaman M, Nokhodchi A. 3D printing for enhanced drug delivery: current state-of-the-art and challenges. Drug Dev Ind Pharm 2020; 46:1385-1401. [DOI: 10.1080/03639045.2020.1801714] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Melissa Wallis
- School of Life Sciences, University of Sussex, Brighton, UK
| | | | | | - Mohammed Maniruzzaman
- Pharmaceutical Engineering and 3D Printing (PharmE3D) Lab, Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, Austin, TX, USA
| | - Ali Nokhodchi
- School of Life Sciences, University of Sussex, Brighton, UK
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17
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Nguyen TT, Oh Y, Kim Y, Shin Y, Baek SK, Park JH. Progress in microneedle array patch (MAP) for vaccine delivery. Hum Vaccin Immunother 2020; 17:316-327. [PMID: 32667239 PMCID: PMC7872046 DOI: 10.1080/21645515.2020.1767997] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A microneedle array patch (MAP) has been developed as a new delivery system for vaccines. Preclinical and clinical trials with a vaccine MAP showed improved stability, safety, and immunological efficacy compared to conventional vaccine administration. Various vaccines can be delivered with a MAP. Currently, microneedle manufacturers can mass-produce pharmaceutical MAP and cosmetic MAP and this mass-production system can be adapted to produce a vaccine MAP. Clinical trials with a vaccine MAP have shown comparable efficacy with conventional administration, and discussions about regulations for a vaccine MAP are underway. However, there are concerns of reasonable cost, mass production, efficacy, and safety standards that meet FDA approval, as well as the need for feedback regarding the best method of administration. Currently, microneedles have been studied for the delivery of many kinds of vaccines, and preclinical and clinical studies of vaccine microneedles are in progress. For the foreseeable future, some vaccines will continue to be administered with syringes and needles while the use of a vaccine MAP continues to be improved because of the advantages of less pain, self-administration, improved stability, convenience, and safety.
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Affiliation(s)
- Thuy Trang Nguyen
- Faculty of Pharmacy, Ho Chi Minh City University of Technology-HUTECH , Ho Chi Minh, Vietnam
| | - Yujeong Oh
- Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University , Seongnam, Republic of Korea
| | - Yunseo Kim
- Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University , Seongnam, Republic of Korea
| | - Yura Shin
- Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University , Seongnam, Republic of Korea
| | - Seung-Ki Baek
- QuadMedicine R&D Centre, QuadMedicine Inc , Seongnam, Republic of Korea
| | - Jung-Hwan Park
- Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University , Seongnam, Republic of Korea
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18
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Leone M, Romeijn S, Du G, Le Dévédec S, Vrieling H, O'Mahony C, Bouwstra J, Kersten G. Diphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administration. Int J Pharm 2020; 580:119182. [DOI: 10.1016/j.ijpharm.2020.119182] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 02/25/2020] [Accepted: 02/25/2020] [Indexed: 12/13/2022]
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19
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Leone M, Romeijn S, Slütter B, O’Mahony C, Kersten G, Bouwstra JA. Hyaluronan molecular weight: Effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigen. Eur J Pharm Sci 2020; 146:105269. [DOI: 10.1016/j.ejps.2020.105269] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 02/11/2020] [Accepted: 02/16/2020] [Indexed: 12/31/2022]
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20
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Pielenhofer J, Sohl J, Windbergs M, Langguth P, Radsak MP. Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery. Front Immunol 2020; 11:266. [PMID: 32174915 PMCID: PMC7055421 DOI: 10.3389/fimmu.2020.00266] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2019] [Accepted: 02/03/2020] [Indexed: 12/31/2022] Open
Abstract
Transcutaneous immunization (TCI) via needle-free and non-invasive drug delivery systems is a promising approach for overcoming the current limitations of conventional parenteral vaccination methods. The targeted access to professional antigen-presenting cell (APC) populations within the skin, such as Langerhans cells (LCs), various dermal dendritic cells (dDCs), macrophages, and others makes the skin an ideal vaccination site to specifically shape immune responses as required. The stratum corneum (SC) of the skin is the main penetration barrier that needs to be overcome by the vaccine components in a coordinated way to achieve optimal access to dermal APC populations that induce priming of T-cell or B-cell responses for protective immunity. While there are numerous approaches to penetrating the SC, such as electroporation, sono- or iontophoresis, barrier and ablative methods, jet and powder injectors, and microneedle-mediated transport, we will focus this review on the recent progress made in particle-based systems for TCI. This particular approach delivers vaccine antigens together with adjuvants to perifollicular APCs by diffusion and deposition in hair follicles. Different delivery systems including nanoparticles and lipid-based systems, for example, solid nano-emulsions, and their impact on immune cells and generation of a memory effect are discussed. Moreover, challenges for TCI are addressed, including timely and targeted delivery of antigens and adjuvants to APCs within the skin as well as a deeper understanding of the ill-defined mechanisms leading to the induction of effective memory responses.
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Affiliation(s)
- Jonas Pielenhofer
- Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-University, Mainz, Germany
| | - Julian Sohl
- Third Department of Medicine - Hematology, Oncology, Pneumology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Maike Windbergs
- Institute of Pharmaceutical Technology, Buchmann Institute for Molecular Life Sciences, Goethe-University, Frankfurt, Germany
| | - Peter Langguth
- Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-University, Mainz, Germany
| | - Markus P Radsak
- Third Department of Medicine - Hematology, Oncology, Pneumology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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21
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Badizadegan K, Goodson JL, Rota PA, Thompson KM. The potential role of using vaccine patches to induce immunity: platform and pathways to innovation and commercialization. Expert Rev Vaccines 2020; 19:175-194. [PMID: 32182145 PMCID: PMC7814398 DOI: 10.1080/14760584.2020.1732215] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/12/2020] [Indexed: 01/14/2023]
Abstract
Introduction: In the last two decades, the evidence related to using vaccine patches with multiple short projections (≤1 mm) to deliver vaccines through the skin increased significantly and demonstrated their potential as an innovative delivery platform.Areas covered: We review the vaccine patch literature published in English as of 1 March 2019, as well as available information from key stakeholders related to vaccine patches as a platform. We identify key research topics related to basic and translational science on skin physical properties and immunobiology, patch development, and vaccine manufacturing.Expert opinion: Currently, vaccine patch developers continue to address some basic science and other platform issues in the context of developing a potential vaccine patch presentation for an existing or new vaccine. Additional clinical data and manufacturing experience could shift the balance toward incentivizing existing vaccine manufactures to further explore the use of vaccine patches to deliver their products. Incentives for innovation of vaccine patches differ for developed and developing countries, which will necessitate different strategies (e.g. public-private partnerships, push, or pull mechanisms) to support the basic and applied research needed to ensure a strong evidence base and to overcome translational barriers for vaccine patches as a delivery platform.
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Affiliation(s)
| | - James L Goodson
- Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Paul A Rota
- Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
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22
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Mao J, Wang H, Xie Y, Fu Y, Li Y, Liu P, Du H, Zhu J, Dong L, Hussain M, Li Y, Zhang L, Zhu J, Tao J. Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis. J Mater Chem B 2020; 8:928-934. [PMID: 31912081 DOI: 10.1039/c9tb00912d] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 μm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion ex vivo. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.
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Affiliation(s)
- Jinzhu Mao
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Hua Wang
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Ying Xie
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Yangxue Fu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Yuce Li
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Pei Liu
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Hongyao Du
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Jinjin Zhu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Liyun Dong
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Mubashir Hussain
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Yan Li
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
| | - Lianbin Zhang
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Jintao Zhu
- Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
| | - Juan Tao
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
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23
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Rodgers AM, Cordeiro AS, Donnelly RF. Technology update: dissolvable microneedle patches for vaccine delivery. MEDICAL DEVICES-EVIDENCE AND RESEARCH 2019; 12:379-398. [PMID: 31572025 PMCID: PMC6756839 DOI: 10.2147/mder.s198220] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 08/08/2019] [Indexed: 12/17/2022] Open
Abstract
Despite vaccination representing one of the greatest advances of modern preventative medicine, there remain significant challenges in vaccine distribution, delivery and compliance. Dissolvable microarray patches or dissolving microneedles (DMN) have been proposed as an innovative vaccine delivery platform that could potentially revolutionize vaccine delivery and circumvent many of the challenges faced with current vaccine strategies. DMN, due to their ease of use, lack of elicitation of pain response, self-disabling nature and ease of transport and distribution, offer an attractive delivery option for vaccines. Additionally, as DMN inherently targets the uppermost skin layers, they facilitate improved vaccine efficacy, due to direct targeting of skin antigen-presenting cells. A plethora of publications have demonstrated the efficacy of DMN vaccination for a range of vaccines, with influenza receiving particular attention. However, before the viable adoption of DMN for vaccination purposes in a clinical setting, a number of fundamental questions must be addressed. Accordingly, this review begins by introducing some of the key barriers faced by current vaccination approaches and how DMN can overcome these challenges. We introduce some of the recent advances in the field of DMN technology, highlighting the potential impact DMN could have, particularly in countries of the developing world. We conclude by reflecting on some of the key questions that remain unanswered and which warrant further investigation before DMNs can be utilized in clinical settings.
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Affiliation(s)
- Aoife M Rodgers
- School of Pharmacy, Queen’s University Belfast, Belfast, BT9 7BL, UK
| | - Ana Sara Cordeiro
- School of Pharmacy, Queen’s University Belfast, Belfast, BT9 7BL, UK
| | - Ryan F Donnelly
- School of Pharmacy, Queen’s University Belfast, Belfast, BT9 7BL, UK
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24
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Du N, Li XH, Bao WG, Wang B, Xu G, Wang F. Resveratrol‑loaded nanoparticles inhibit enterovirus 71 replication through the oxidative stress‑mediated ERS/autophagy pathway. Int J Mol Med 2019; 44:737-749. [PMID: 31173159 DOI: 10.3892/ijmm.2019.4211] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 05/23/2019] [Indexed: 11/05/2022] Open
Abstract
A number of studies have demonstrated that resveratrol (RES) has a variety of biological functions, including cardiovascular protective effects, treatment of mutations, and anti‑inflammatory, anti‑tumor and antiviral effects. In the present study, RES‑loaded nanoparticles (RES‑NPs) were used to protect rhabdosarcoma (RD) cells from enterovirus 71 (EV71) infection, and the relevant mechanisms were also explored. An amphiphilic copolymer, monomethoxy poly (ethylene glycol)‑b‑poly (D,L‑lactide), was used as vehicle material, and RES‑NPs with necessitated drug‑loading content and suitable sizes were prepared under optimized conditions. RES‑NPs exhibited the ability to inhibit the increase of intracellular oxidative stress. The prospective mechanism for the function of RES‑NPs suggested was that RES‑NPs may inhibit the oxidative stress‑mediated PERK/eIF2α/ATF4 signaling pathway, downregulate the autophagy pathway and resist EV71‑induced RD cells injury. Furthermore, RES‑NPs treatment markedly inhibited the secretion of inflammatory factors, including interleukin (IL)‑6, IL‑8 and tumor necrosis factor‑α elicited by EV71 infection. Concomitantly, inhibitors of oxidative stress, endoplasmic reticulum stress (ERS) or autophagy were demonstrated to negate the anti‑inflammatory and antiviral effects of RES‑NPs on EV71‑infected RD cells. These results demonstrated that RES‑NPs attenuated EV71‑induced viral replication and inflammatory effects by inhibiting the oxidative stress‑mediated ERS/autophagy signaling pathway. In view of their safety and efficiency, these RES‑NPs have potential applications in protecting RD cells from EV71 injury.
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Affiliation(s)
- Na Du
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Xiao-Hua Li
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wan-Guo Bao
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Bin Wang
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Guang Xu
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Feng Wang
- Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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25
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Liu S, Zhang S, Duan Y, Niu Y, Gu H, Zhao Z, Zhang S, Yang Y, Wang X, Gao Y, Yang P. Transcutaneous immunization of recombinant Staphylococcal enterotoxin B protein using a dissolving microneedle provides potent protection against lethal enterotoxin challenge. Vaccine 2019; 37:3810-3819. [PMID: 31147275 DOI: 10.1016/j.vaccine.2019.05.055] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 05/16/2019] [Accepted: 05/19/2019] [Indexed: 12/25/2022]
Abstract
Staphylococcal enterotoxin B (SEB) produced by the Staphylococcus aureus bacteriumis most commonly associated with food poisoning and is known to also cause toxic shock syndrome. Currently, no approved vaccine or specific drug is available to treat SEB intoxication. In this study, we fabricated dissolving microneedles (MNs) loaded with recombinant SEB (rSEB) protein, and evaluated its characteristics, including dissolution profile, protein particle size, insertion depth, antigen retention time in vivo, and skin irritation. Our results showed that rSEB protein-loaded dissolving MNs made of chondroitin sulfate (2%) and trehalose (0.8%) could easily penetrate into the mouse skin within 5 min. The rSEB particle size was unchanged before and after MN fabrication. The skin penetration depth of the MNs was 260 µm. Moreover, the MNs also significantly extended the antigen retention time in vivo. rSEB protein-loaded dissolving MNs also triggered slight erythema at the beginning of administration, but this erythema disappeared within a few hours. More importantly, we investigated the immunogenicity and protective efficacy of rSEB protein-loaded dissolving MNs. Challenge studies in mice revealed that mice in full-dose MN group had a high level of SEB specific antibody response thatprovided100% protection against a lethal SEB toxin challenge. However, there was only 60% protection observed in mice that were in the half-dose MN (dose sparing) group. We also determined the pathological alterations in the tissues of the immunized mice. Taken together, these dissolving MNs may present a promising transcutaneous immunization strategy for treating SEB intoxication.
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Affiliation(s)
- Siqi Liu
- Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital, Beijing 100039, China; College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, China
| | - Suohui Zhang
- Key Laboratory of Photo Chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing China
| | - Yueqiang Duan
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
| | - Yan Niu
- College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, China
| | - Hongjing Gu
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
| | - Zhongpeng Zhao
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
| | - Shaogeng Zhang
- Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital, Beijing 100039, China
| | - Ying Yang
- College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010110, China
| | - Xiliang Wang
- State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
| | - Yunhua Gao
- Key Laboratory of Photo Chemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing China.
| | - Penghui Yang
- Beijing 302 Hospital/5th Medical Center of Chinese PLA General of Hospital, Beijing 100039, China; State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
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26
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Ren G, Ding G, Zhang H, Wang H, Jin Z, Yang G, Han Y, Zhang X, Li G, Li W. Antiviral activity of sophoridine against enterovirus 71 in vitro. JOURNAL OF ETHNOPHARMACOLOGY 2019; 236:124-128. [PMID: 30853644 DOI: 10.1016/j.jep.2019.02.045] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 02/25/2019] [Accepted: 02/25/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Enterovirus 71 (EV71) has a propensity to cause hand-foot-and-mouth disease (HFMD) epidemics associated with neurological sequelae. Unfortunately, no drugs are currently available for the clinical treatment of EV71 infections. Sophoridine (SRI) is one of the most abundant alkaloids in Sophora flavescens Aiton (Leguminosae), which has been used to treat fever, throat inflammation, cancer, and other diseases. MATERIALS AND METHODS In this study, we found that SRI inhibits EV71 infection in Vero cells. To study the antiviral activity of SRI, Vero cells were divided into 3 treatment groups based on the timing of SRI dosing: prior to viral adsorption (Group A), during viral adsorption (Group B), and after viral adsorption (Group C). We further revealed the antiviral activity of SRI with the attachment assay and the penetration assay. For Group A, 50% viability of Vero cells was observed at a SRI concentration of 61.39 μg/mL, whereas for Groups B, 50% viability was observed at SRI concentrations of 196.86 μg/mL. Furthermore, 29.7% cell viability was observed even at a SRI concentration of 1000 μg/mL in Groups C. The results show that SRI was highly effective against EV71 when Vero cells were pretreated with SRI for 2 h (Group A). Further researches indicate SRI was highly effective at inhibiting EV71 attachment when the SRI concentrations over 250 μg/mL (P < 0.001). CONCLUSIONS We have shown that Vero cell viability increases when SRI is administered prior to viral adsorption. This suggests that SRI has the considerable potential as an antiviral for EV71 disease prevention.
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Affiliation(s)
- Gang Ren
- Affiliated Hospital of Hebei Engineering University, Hebei, 056000, China
| | - Guotao Ding
- Handan Municipal Center for Disease Control and Prevention, Hebei, 056000, China
| | - Hongyan Zhang
- Affiliated Hospital of Hebei Engineering University, Hebei, 056000, China
| | - Haipeng Wang
- School of Life Science and Technology, Tongji University, Shanghai, 200092, China
| | - Zengjun Jin
- Handan Municipal Center for Disease Control and Prevention, Hebei, 056000, China; Hebei Engineering University, Hebei, 056000, China
| | - Guoxing Yang
- Handan Municipal Center for Disease Control and Prevention, Hebei, 056000, China
| | - Yonghong Han
- Handan Municipal Center for Disease Control and Prevention, Hebei, 056000, China
| | - Xia Zhang
- School of Life Science and Technology, Tongji University, Shanghai, 200092, China
| | - Guiying Li
- Affiliated Hospital of Hebei Engineering University, Hebei, 056000, China.
| | - Weihao Li
- Handan Municipal Center for Disease Control and Prevention, Hebei, 056000, China.
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A compendium of current developments on polysaccharide and protein-based microneedles. Int J Biol Macromol 2019; 136:704-728. [PMID: 31028807 DOI: 10.1016/j.ijbiomac.2019.04.163] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 01/14/2023]
Abstract
Microneedles (MNs), i.e. minimally invasive three-dimensional microstructures that penetrate the stratum corneum inducing relatively little or no pain, have been studied as appealing therapeutic vehicles for transdermal drug delivery. Over the last years, the fabrication of MNs using biopolymers, such as polysaccharides and proteins, has sparked the imagination of scientists due to their recognized biocompatibility, biodegradability, ease of fabrication and sustainable character. Owing to their wide range of functional groups, polysaccharides and proteins enable the design and preparation of materials with tunable properties and functionalities. Therefore, these biopolymer-based MNs take a revolutionary step offering great potential not only in drug administration, but also in sensing and response to physiological stimuli. In this review, a critical and comprehensive overview of the polysaccharides and proteins employed in the design and engineering of MNs will be given. The strategies adopted for their preparation, their advantages and disadvantages will be also detailed. In addition, the potential and challenges of using these matrices to deliver drugs, vaccines and other molecules will be discussed. Finally, this appraisal ends with a perspective on the possibilities and challenges in research and development of polysaccharide and protein MNs, envisioning the future advances and clinical translation of these platforms as the next generation of drug delivery systems.
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28
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Chiu YH, Chen MC, Wan SW. Sodium Hyaluronate/Chitosan Composite Microneedles as a Single-Dose Intradermal Immunization System. Biomacromolecules 2018; 19:2278-2285. [DOI: 10.1021/acs.biomac.8b00441] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Yu-Hsiu Chiu
- Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan 701
| | - Mei-Chin Chen
- Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan 701
| | - Shu-Wen Wan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan 840
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29
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Luzuriaga MA, Berry DR, Reagan JC, Smaldone RA, Gassensmith JJ. Biodegradable 3D printed polymer microneedles for transdermal drug delivery. LAB ON A CHIP 2018. [PMID: 29536070 DOI: 10.1039/c8lc00098k] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/05/2023]
Abstract
Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.
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Affiliation(s)
- Michael A Luzuriaga
- Department of Chemistry and Biochemistry, University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080-3021, USA.
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Sanjay ST, Zhou W, Dou M, Tavakoli H, Ma L, Xu F, Li X. Recent advances of controlled drug delivery using microfluidic platforms. Adv Drug Deliv Rev 2018; 128:3-28. [PMID: 28919029 PMCID: PMC5854505 DOI: 10.1016/j.addr.2017.09.013] [Citation(s) in RCA: 190] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 08/11/2017] [Accepted: 09/13/2017] [Indexed: 12/13/2022]
Abstract
Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery.
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Affiliation(s)
- Sharma T. Sanjay
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
| | - Wan Zhou
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
| | - Maowei Dou
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
- Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory
| | - Hamed Tavakoli
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
| | - Lei Ma
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
| | - Feng Xu
- Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, P.R. China
| | - XiuJun Li
- Department of Chemistry, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
- Border Biomedical Research Center, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
- Biomedical Engineering, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
- Environmental Science and Engineering, University of Texas at El Paso, 500 West University Ave, El Paso, Texas, 79968, USA, Richland, Washington, 99354, USA
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31
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Insulin delivery systems combined with microneedle technology. Adv Drug Deliv Rev 2018; 127:119-137. [PMID: 29604374 DOI: 10.1016/j.addr.2018.03.011] [Citation(s) in RCA: 181] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/22/2018] [Accepted: 03/26/2018] [Indexed: 11/24/2022]
Abstract
Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and poke" and "poke and release" approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation.
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32
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Lee H, Song C, Baik S, Kim D, Hyeon T, Kim DH. Device-assisted transdermal drug delivery. Adv Drug Deliv Rev 2018; 127:35-45. [PMID: 28867296 DOI: 10.1016/j.addr.2017.08.009] [Citation(s) in RCA: 201] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 08/19/2017] [Accepted: 08/29/2017] [Indexed: 12/31/2022]
Abstract
Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted.
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Affiliation(s)
- Hyunjae Lee
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
| | - Changyeong Song
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Seungmin Baik
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Dokyoon Kim
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
| | - Taeghwan Hyeon
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
| | - Dae-Hyeong Kim
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
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33
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Production and purification of virus-like particles of different enterovirus subtypes as vaccines. J Taiwan Inst Chem Eng 2018. [DOI: 10.1016/j.jtice.2017.10.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Chen Z, Lv Y, Qi J, Zhu Q, Lu Y, Wu W. Overcoming or circumventing the stratum corneum barrier for efficient transcutaneous immunization. Drug Discov Today 2018; 23:181-186. [DOI: 10.1016/j.drudis.2017.09.017] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 09/20/2017] [Accepted: 09/27/2017] [Indexed: 10/18/2022]
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35
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Leone M, Mönkäre J, Bouwstra JA, Kersten G. Dissolving Microneedle Patches for Dermal Vaccination. Pharm Res 2017; 34:2223-2240. [PMID: 28718050 PMCID: PMC5643353 DOI: 10.1007/s11095-017-2223-2] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 06/26/2017] [Indexed: 12/31/2022]
Abstract
The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (e.g. pain, needle-stick injuries or needle re-use). This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antigen. The microneedle patch fabrication techniques and their challenges are discussed as well as the microneedle characterization methods and antigen stability aspects. The immunogenicity of antigens formulated in dissolving microneedles are addressed. Finally, the early clinical development is discussed.
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Affiliation(s)
- M Leone
- Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, the Netherlands
| | - J Mönkäre
- Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, the Netherlands
| | - J A Bouwstra
- Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, the Netherlands.
| | - G Kersten
- Division of Drug Delivery Technology, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P.O. Box 9502, 2300 RA, Leiden, the Netherlands.,Department of Analytical Development and Formulation, Intravacc, Bilthoven, the Netherlands
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36
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Li M, Duan Y, Yang X, Yang Q, Pang B, Wang Y, Ren T, Wang X, Zhao Z, Liu S. Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine. Vaccine 2017; 35:3709-3717. [DOI: 10.1016/j.vaccine.2017.05.060] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Revised: 05/14/2017] [Accepted: 05/20/2017] [Indexed: 10/19/2022]
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