Transdermal Drug Delivery Systems: Recent Advances in Nanocarriers, Microneedles, and Controlled Release Technologies
DOI:
https://doi.org/10.69980/xnb31v19Keywords:
Controlled release, Microneedles, Nanocarriers, Skin permeation, Transdermal drug deliveryAbstract
Transdermal drug delivery has progressed from conventional passive patches to increasingly sophisticated systems incorporating nanocarriers, microneedles, smart materials, and controlled-release technologies. Broader clinical use, however, remains limited by the barrier properties of the stratum corneum and by the poor permeability of hydrophilic compounds, macromolecules, and many therapeutically important drugs. This review evaluates recent advances in transdermal drug delivery, with particular emphasis on nanocarrier-based systems, microneedle technologies, integrated nanocarrier–microneedle platforms, and responsive controlled-release approaches. Recent literature was narratively synthesised to assess their mechanisms, formulation characteristics, therapeutic applications, translational potential, and current limitations. The available evidence indicates that nanocarriers can improve drug solubility, stability, cutaneous interaction, and localised deposition, whereas microneedles can transiently bypass the stratum corneum and facilitate delivery of peptides, proteins, vaccines, and other poorly permeable agents. Hybrid systems may further enhance intradermal targeting and prolong drug release, while polymeric matrices, hydrogels, reservoir systems, and stimuli-responsive platforms can provide greater temporal control over dosing. Translation into routine clinical practice remains constrained by manufacturing reproducibility, dose uniformity, skin compatibility, device reliability, sterility, scalability, long-term safety, and regulatory complexity. Overall, these technologies are redefining transdermal delivery as a multifunctional therapeutic platform, but their clinical value will depend on standardised performance testing, scalable manufacturing, and robust human validation.
References
1. Abdul Aziz, A. F., Beh, Y. Q., Farahiyah, I. I., Azmir, S. S., Kee, P. E., Uddin, A. H., & Liew, K. B. (2025). A review on the mechanisms, applications, and clinical trials of advanced technologies in the transdermal drug delivery system. Current Pharmaceutical Biotechnology, 26(12), 1971-1985.
2. Ahmad, N. N., Ghazali, N. N. N., & Wong, Y. H. (2021). Concept design of transdermal microneedles for diagnosis and drug delivery: A review. Advanced Engineering Materials, 23(12), 2100503.
3. Alkilani, A. Z., Nasereddin, J., Hamed, R., Nimrawi, S., Hussein, G., Abo-Zour, H., & Donnelly, R. F. (2022). Beneath the skin: a review of current trends and prospects of transdermal drug delivery systems. Pharmaceutics, 14(6), 1152.
4. Avcil, M., & Çelik, A. (2021). Microneedles in drug delivery: progress and challenges. Micromachines, 12(11), 1321.
5. Buzia, O. D., Păduraru, A. M., Stefan, C. S., Dinu, M., Cocoș, D. I., Nwabudike, L. C., & Tatu, A. L. (2023). Strategies for improving transdermal administration: new approaches to controlled drug release. Pharmaceutics, 15(4), 1183.
6. Cammarano, A., Dello Iacono, S., Meglio, C., & Nicolais, L. (2023). Advances in transdermal drug delivery systems: a bibliometric and patent analysis. Pharmaceutics, 15(12), 2762.
7. Damiri, F., Kommineni, N., Ebhodaghe, S. O., Bulusu, R., Jyothi, V. G. S., Sayed, A. A., ... & Berrada, M. (2022). Microneedle-based natural polysaccharide for drug delivery systems (DDS): progress and challenges. Pharmaceuticals, 15(2), 190.
8. de Araujo, D. R., & Padula, C. (2023). Topical drug delivery: innovative controlled release systems. Pharmaceutics, 15(6), 1716.
9. Dumitriu Buzia, O., Păduraru, A. M., Stefan, C. S., Dinu, M., Cocoș, D. I., Nwabudike, L. C., & Tatu, A. L. (2023). Strategies for improving transdermal administration: new approaches to controlled drug release. Pharmaceutics, 15(4), 1183.
10. Jeong, W. Y., Kwon, M., Choi, H. E., & Kim, K. S. (2021). Recent advances in transdermal drug delivery systems: a review. Biomaterials research, 25(1), 24.
11. Kang, Y., Zhang, S., Wang, G., Yan, Z., Wu, G., Tang, L., & Wang, W. (2024). Nanocarrier-based transdermal drug delivery systems for dermatological therapy. Pharmaceutics, 16(11), 1384.
12. Kathuria, T., Saharan, R., Dhankhar, S., Mahajan, S., Beniwal, S. K., Chauhan, S., ... & Yasmin, S. (2025). Transdermal drug delivery systems: Integrating modern technology for enhanced therapeutics. Current Drug Safety.
13. Liu, S., Deng, T., Cheng, H., Lu, J., & Wu, J. (2025). Advances in transdermal drug delivery systems and clinical applications in inflammatory skin diseases. Pharmaceutics, 17(6), 746.
14. Mdanda, S., Ubanako, P., Kondiah, P. P., Kumar, P., & Choonara, Y. E. (2021). Recent advances in microneedle platforms for transdermal drug delivery technologies. Polymers, 13(15), 2405.
15. Meng, F., Qiao, X., Xin, C., Ju, X., & He, M. (2024). Recent progress of polymeric microneedle-assisted long-acting transdermal drug delivery. Journal of Pharmacy & Pharmaceutical Sciences, 27, 12434.
16. Nguyen, H. X., & Nguyen, C. N. (2023). Microneedle-mediated transdermal delivery of biopharmaceuticals. Pharmaceutics, 15(1), 277.
17. Oh, S. J., & Jung, J. H. (2022). Sustainable drug release using nanoparticle encapsulated microneedles. Chemistry–An Asian Journal, 17(16), e202200333.
18. Panda, P., Mohanty, T., & Mohapatra, R. (2025). Advancements in transdermal drug delivery systems: harnessing the potential of macromolecular assisted permeation enhancement and novel techniques. Aaps Pharmscitech, 26(1), 29.
19. Peña-Juárez, M. C., Guadarrama-Escobar, O. R., & Escobar-Chávez, J. J. (2022). Transdermal delivery systems for biomolecules. Journal of Pharmaceutical Innovation, 17(2), 319-332.
20. Qu, F., Geng, R., Liu, Y., & Zhu, J. (2022). Advanced nanocarrier-and microneedle-based transdermal drug delivery strategies for skin diseases treatment. Theranostics, 12(7), 3372.
21. Queiroz, M. L. B., Shanmugam, S., Santos, L. N. S., Campos, C. D. A., Santos, A. M., Batista, M. S., ... & Serafini, M. R. (2020). Microneedles as an alternative technology for transdermal drug delivery systems: a patent review. Expert opinion on therapeutic patents, 30(6), 433-452.
22. Rabiei, M., Kashanian, S., Samavati, S. S., Jamasb, S., & McInnes, S. J. (2020). Nanomaterial and advanced technologies in transdermal drug delivery. Journal of drug targeting, 28(4), 356-367.
23. Raina, N., Rani, R., Thakur, V. K., & Gupta, M. (2023). New insights in topical drug delivery for skin disorders: from a nanotechnological perspective. ACS omega, 8(22), 19145.
24. Ramadon, D., McCrudden, M. T., Courtenay, A. J., & Donnelly, R. F. (2022). Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug delivery and translational research, 12(4), 758-791.
25. Roy, S. K., Ali, K. A., Biswas, M., Dey, A., Bishal, A., & Kuiry, A. (2025). Microneedles: an efficient technique to increase transdermal drug delivery system. Current drug delivery, 22(7), 878-894.
26. Ruan, S., Zhang, Y., & Feng, N. (2021). Microneedle-mediated transdermal nanodelivery systems: a review. Biomaterials Science, 9(24), 8065-8089.
27. Sabbagh, F., Zakrzewska, A., Rybak, D., Król, J., Abdi, A., Nakielski, P., & Pierini, F. (2025). Transdermal drug delivery systems powered by artificial intelligence. Advanced Healthcare Materials, 14(32), e03030.
28. Seetharam, A. A., Choudhry, H., Bakhrebah, M. A., Abdulaal, W. H., Gupta, M. S., Rizvi, S. M. D., ... & Moin, A. (2020). Microneedles drug delivery systems for treatment of cancer: a recent update. Pharmaceutics, 12(11), 1101.
29. Singh, T., Arora, A., Sahu, K. K., Patel, P., Kaur, S., Thakur, S., ... & Kurmi, B. D. (2024). A complete sojourn of recent advancements and applications in transdermal drug delivery systems. Journal of Drug Delivery Science and Technology, 102, 106328.
30. Swain, S., Singh, A. P., & Yadav, R. K. (2022). A review on polymer hydrogel and polymer microneedle based transdermal drug delivery system. Materials Today: Proceedings, 61, 1061-1066.
31. Tapfumaneyi, P., Imran, M., Mohammed, Y., & Roberts, M. S. (2022). Recent advances and future prospective of topical and transdermal delivery systems. Frontiers in Drug Delivery, 2, 957732.
32. Udugade, S., Udugade, B. V., Patil, S. R., Utage, A. C., & Swaroop, S. (2025). Nanotechnology-enhanced transdermal systems for infectious diseases. Current Opinion in Pharmacology, 84, 102547.
33. Wang, Y., He, Y., Zhang, T., & Lin, Y. (2025). Advances in microneedle technology for skin wound healing: integrating nanomaterials and intelligent drug delivery systems. Nanoscale, 17(32), 18505-18533.
34. Wong, W. F., Ang, K. P., Sethi, G., & Looi, C. Y. (2023). Recent advancement of medical patch for transdermal drug delivery. Medicina, 59(4), 778.
35. Wu, Y., Ieong, H., Wang, W., Wu, C., Lu, A., Pan, X., & Huang, Z. (2025). Polymer modification effects in nanocarrier-loaded dissolving microneedles: implications for transdermal drug delivery. Chinese Chemical Letters, 111944.
36. Xu, F., Qiu, Z., Zhang, M., Ren, Y., Kong, L., Liu, Y., ... & Wang, P. (2025). Transdermal drug delivery systems: a comprehensive review of mechanisms, technologies, and clinical applications. Pharmaceutical Research, 42(12), 2429-2442.
37. Zafar, S., Rana, S. J., Hamza, M., Hussain, A., Abbas, N., Ghori, M. U., & Arshad, M. S. (2025). Advancements in transdermal drug delivery using microneedles: technological and material perspective. Discover Pharmaceutical Sciences, 1(1), 5.
38. Zarepour, A., Soozanipour, A., & Khosravi, A. (2025). Microneedle-assisted nanomedicine: Emerging strategies for transdermal drug delivery. Current Opinion in Biomedical Engineering, 35, 100602.
39. Zhang, H., Pan, Y., Hou, Y., Li, M., Deng, J., Wang, B., & Hao, S. (2024). Smart physical‐based transdermal drug delivery system: towards intelligence and controlled release. Small, 20(9), 2306944.
Zhao, Y., Xiu, R., Wang, C., Wang, J., Guo, D., Luo, W., ... & Gao, X. (2025). Nanoformulation-based transdermal drug delivery: a paradigm shift in antiparasitic therapy for zoonotic diseases. Pharmaceutics, 17(9), 1216.
