Advances in Transdermal Drug Delivery: The Development of Microneedle Technology for Improved Therapeutic Outcomes
DOI:
https://doi.org/10.55544/jrasb.3.5.21Keywords:
Transdermal Drug Delivery Systems, Microneedle Technology, 4D microneedles, Laser cutting, FDA and EMA regulatory challengesAbstract
Transdermal Drug Delivery Systems (TDDS) represent a significant advancement in therapeutic administration by allowing drugs to bypass the gastrointestinal system and first-pass hepatic metabolism, enhancing patient compliance, and enabling sustained drug release. However, traditional TDDS face limitations, including resistance from the skin's natural barrier and limited efficacy in delivering large or hydrophilic molecules. Microneedle (MN) technology offers a breakthrough solution, using minimally invasive micron-sized needles to bypass the stratum corneum, facilitating efficient drug delivery without significant pain or discomfort. This review explores the evolution and recent advancements in microneedle technology, highlighting its role in overcoming the limitations of conventional TDDS. Microneedles have been shown to enhance drug bioavailability, reduce side effects, and expand the range of deliverable therapeutics, including vaccines, insulin, and genetic materials. The development of bioinspired 4D microneedles further extends their application to diagnostics and cosmetic treatments, positioning MNs as a versatile tool in modern medicine. Key sections of the review focus on the types of microneedles—solid, coated, dissolving, hollow, and hydrogel-forming—and their respective fabrication methods, materials, and drug delivery mechanisms. The review also discusses the challenges related to scaling up production, ensuring consistent quality, and regulatory hurdles in achieving clinical approval. Future directions include the integration of microneedles with nanotechnology, combination therapies, and sustainable design, particularly in developing regions where biodegradable materials may address environmental and disposal concerns. The potential for microneedle technology to revolutionize transdermal drug delivery, diagnostics, and therapeutic monitoring is significant, with ongoing research paving the way for multifunctional applications that can reshape patient care and treatment modalities.
Downloads
Metrics
References
Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3(2):115-24.
Venkatraman S, Gale R. Skin adhesives and skin adhesion. J Invest Dermatol. 2013;133(4):1497-504.
Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin's barrier function. Pharm Sci Technol Today. 2000;3(9):318-26.
Prausnitz MR. Microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56(5):581-7.
Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004;56(5):619-58.
Brown MB, Martin GP, Jones SA, Akomeah FK. Dermal and transdermal drug delivery systems: current and future prospects. Drug Deliv. 2006;13(3):175-87.
Gupta J, Felner EI, Prausnitz MR. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol Ther. 2009;11(6):329-37.
Langer R. Transdermal drug delivery: past progress, current status, and future prospects. Adv Drug Deliv Rev. 2004;56(5):557-8.
Benson HA. Transdermal drug delivery: penetration enhancement techniques. Curr Drug Deliv. 2005;2(1):23-33.
Cevc G, Vierl U. Nanotechnology and the transdermal route: A state of the art review and critical appraisal. J Control Release. 2010;141(3):277-99.
Ali M, Namjoshi S, Phan K, et al. 3D Printed Microneedles for the Transdermal Delivery of NAD+ Precursor: Toward Personalization of Skin Delivery. ACS Biomaterials. 2024.
Hu W. Fabrication of Silicon Out-of-Plane Microneedles for Potential Drug Delivery and Interstitial Fluid Extraction. uwaterloo.ca. 2024.
Supe AR, Nemmaniwar A, Dhaneshwar G, et al. Emerging Era of Microneedle Technology for Transdermal Drug Delivery System. iipseries.org. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Maia M, Jesus S, Borges O. Optimizing Insulin Therapy: Are Microneedles a Viable Alternative to Subcutaneous Insulin Injection? Journal of Drug Delivery Science and Technology. 2024.
Park JH, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release. 2005;104(1):51-66.
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261-1268.
Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117(2):227-237.
Sullivan SP, Murthy N, Prausnitz MR. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv Mater. 2008;20(5):933-938.
Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64(14):1547-1568.
Lee K, Lee CY, Jung H. Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials. 2011;32(11):3134-3140.
McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A. 2003;100(24):13755-13760.
Maaden K, Jiskoot W, Bouwstra J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J Control Release. 2012;161(2):645-655.
Donnelly RF, Singh TR, Woolfson AD. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv Transl Res. 2012;2(4):311-321.
Donnelly RF, Moffatt K, Woolfson AD. Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater. 2012;22(23):4879-4890.
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261-1268.
Donnelly RF, Singh TR, Woolfson AD. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv Transl Res. 2012;2(4):311-321.
Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64(14):1547-1568.
Prausnitz MR, Mikszta JA, Cormier M, Andrianov AK. Microneedle-based vaccines. Curr Top Microbiol Immunol. 2009;333:369-393.
McCrudden MT, Alkilani AZ, McCrudden CM, McAlister E, McCarthy HO, Woolfson AD, et al. Design and formulation of dissolving microneedles for transdermal drug delivery of high molecular weight biopharmaceuticals. J Control Release. 2015;209:162-172.
Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87(8):922-925.
Hirobe S, Azukizawa H, Hanafusa T, Matsuo K, Quan YS, Kamiyama F, et al. Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. Biomaterials. 2015;57:50-58.
Cormier M, Nomura T, Lee K, Tamada J, Taira M, Langer R, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Release. 2004;97(3):503-511.
Donnelly RF, Singh TR, Woolfson AD. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv Transl Res. 2012;2(4):311-321.
McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A. 2003;100(24):13755-13760.
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261-1268.
Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64(14):1547-1568.
Wilke N, Mulcahy A, Ye SR, Morrissey A. Process optimization and characterization of silicon microneedles fabricated by wet etch technology. Microelectron J. 2005;36(7):650-656.
Khanna P, Luongo K, Strom JA, Bhansali S. Microneedle-based automated therapy for diabetes mellitus. J Diabetes Sci Technol. 2011;5(5):1128-1136.
Lim SH, Kathuria H, Tan JJ, Kang L. 3D printed microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2018;127:23-37.
Xu J, Jin T, Zhang L. Dissolvable microneedles: fabrication, characterization, and transdermal drug delivery. J Control Release. 2018;291:187-191.
Yang H, Wu X, Yin L, Zhou J, Liu Y. Electrochemical microneedles for biosensing. Biosens Bioelectron. 2020;170:112636.
Bal SM, Ding Z, van Riet E, Jiskoot W, Bouwstra JA. Advances in transcutaneous vaccine delivery: do all ways lead to Rome? J Control Release. 2010;148(3):266-282.
Prausnitz MR. Engineering microneedle patches for vaccination and drug delivery to skin. Annu Rev Chem Biomol Eng. 2017;8:177-200.
Duarah S, Sharma M, Wen J. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population. Eur J Pharm Biopharm. 2019;136:48-69.
Liu R, Li A, Lang Y, et al. Stimuli-responsive polymer microneedles: A rising transdermal drug delivery system and its applications in biomedical. J Drug Deliv Sci Technol. 2023;79:104036.
Zhang W, Zhang W, Li C, et al. Recent advances of microneedles and their application in disease treatment. Int J Mol Sci. 2022;23(5):2401.
Queiroz MLB, Shanmugam S, Santos LNS, et al. Microneedles as an alternative technology for transdermal drug delivery systems: A patent review. Expert Opin Ther Pat. 2020;30(5):319-336.
Rajput A, Patil A, Kandhare P, et al. Application of microneedle arrays in cosmetics: Promises, advances, and challenges. Med Nov Technol Dev. 2024;12:100021.
Giri Nandagopal MS, Antony R, et al. Overview of microneedle system: A third-generation transdermal drug delivery approach. Microsyst Technol. 2014;20(8):1527-1539.
Amarnani R, Shende P. Microneedles in diagnostic, treatment and theranostics: An advancement in minimally-invasive delivery systems. Biomed Microdevices. 2022;24(1):1-10.
Yang J, Liu X, Fu Y, et al. Recent advances of microneedles for biomedical applications: Drug delivery and beyond. Acta Pharm Sin B. 2019;9(3):469-483.
Gunda RK, Parameshwar K. Enhancement of Skin Permeability with Microneedles Techniques: From Conceptual Framework to Commercial Products. Nano Bio Letters 2024.
Youden B. The Development and Evaluation of Next-Generation Metallic Nanomedicines for Oncology. University of Waterloo 2024.
Kordyl O, Styrna Z, Wojtyłko M, Michniak-Kohn B. Microneedle-based arrays: Breakthrough strategy for the treatment of bacterial and fungal skin infections. Microbes and Infection 2024.
Prausnitz MR. Engineering microneedle patches for vaccination and drug delivery to skin. Annual Review of Chemical and Biomolecular Engineering 2017.
Bariya SH, Gohel MC, Mehta TA. Microneedles: An emerging transdermal drug delivery system. Journal of Pharmacy and Pharmacology 2012.
Sartawi Z, Blackshields C, Faisal W. Dissolving microneedles: Applications and growing therapeutic potential. Journal of Controlled Release 2022.
Larrañeta E, Lutton REM, Woolfson AD. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture, and commercial development. Materials Science and Engineering 2016.
Nguyen HX, Nguyen CN. Microneedle-mediated transdermal delivery of biopharmaceuticals. Pharmaceutics 2023.
Wang J, Zhang Y, Aghda NH, Pillai AR. Emerging 3D printing technologies for drug delivery devices: Current status and future perspectives. Advanced Drug Delivery Reviews 2021.
Giri Nandagopal MS, Antony R. Overview of microneedle system: a third generation transdermal drug delivery approach. Microsystem Technologies 2014.
Zhao J, Xu G, Yao X, Zhou H, Lyu B, Pei S. Microneedle-based insulin transdermal delivery system: current status and translation challenges. Drug Delivery and Translational Research 2022.
Liu Y, Qu F, Geng R, Zhu J. Advanced nanocarrier-and microneedle-based transdermal drug delivery strategies for skin diseases treatment. Theranostics 2022.
Ganeson K, Murugaiyah V, Alias AH, Amirul AAA. Microneedles for efficient and precise drug delivery in cancer therapy. Pharmaceutics 2023;
Rajput A, Pawar A. Application of Microneedle Arrays in Cosmetics: Promises, Advances, and Challenges. Medicine in Novel Technology 2024.
Wang J, Zhang Y, Aghda NH, Pillai AR. Emerging 3D printing technologies for drug delivery devices: Current status and future perspective. Advanced Drug Delivery Reviews 2021.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Shivshankar M. Nagrik, Vaishnavi S. Akhare, Manisha W. Bhade, Mohini R. Nayse, Ankita G. Gulhane, Shreya P. Bhorkhade, Shatrughna U. Nagrik, Ashwini G. Verulkar
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.