Microagujas inteligentes: el futuro de la liberación transdérmica de fármacos
DOI:
https://doi.org/10.68038/yz6ehg73Palabras clave:
microagujas, hidrogeles, estímulo responsividad, liberación de fármacoResumen
Los parches de microagujas han surgido como un área prometedora en la investigación biomédica, debido a su capacidad de administrar una amplia variedad de fármacos, vacunas y otras sustancias a través de la piel, minimizando el dolor y daño causados por las agujas hipodérmicas. En contraste con las rutas tradicionales como la intravenosa y la oral, las microagujas ofrecen una administración indolora, no invasiva y de fácil autoadministración; además, pueden mejorar la biodisponibilidad de determinados fármacos al evitar el metabolismo hepático de primer paso, asegurando una liberación gradual al torrente sanguíneo que resulta en una menor frecuencia de administración. Estos parches de microagujas, fabricados generalmente a partir de materiales biocompatibles y biodegradables, se subdividen en activos, que permiten controlar la liberación de sustancias mediante estímulos externos, y pasivos, que carecen de esta capacidad. Entre los distintos tipos de microagujas, destacan las de tipo hidrogel, formadas por polímeros inteligentes entrecruzados que forman una red capaz de absorber agua, hincharse y liberar el fármaco en respuesta a diversos estímulos externos como cambios en pH, temperatura, luz, magnetismo, etc., y cuya respuesta puede ser regulada ajustando su composición y grado de entrecruzamiento. Esta revisión tiene como objetivo destacar el potencial de esta tecnología como un sistema novedoso, biocompatible y seguro para la encapsulación de fármaco en dosis terapéuticas, y su liberación controlada ante cambios fisiológicos como el pH, para tratamientos alternativos a enfermedades como melanoma, así como discutir los desafíos actuales y las potenciales aplicaciones en biomedicina.
Referencias
Adamson, A. S., Welch, H., & Welch, H. G. (2022). Association of UV radiation exposure, diagnostic scrutiny, and melanoma incidence in US counties. JAMA Internal Medicine, 182(11), 1181–1189. https://doi.org/10.1001/jamainternmed.2022.4342
Al-Badry, A. S., Al-Mayahy, M. H., & Scurr, D. J. (2023). Enhanced transdermal delivery of acyclovir via hydrogel microneedle arrays. Journal of Pharmaceutical Sciences, 112(4), 1011–1019. https://doi.org/10.1016/j.xphs.2022.11.012
Andrade, F., Roca-Melendres, M. M., Durán-Lara, E. F., Rafael, D., & Schwartz, S., Jr. (2021). Stimuli-responsive hydrogels for cancer treatment: The role of pH, light, ionic strength and magnetic field. Cancers, 13(5), 1164. https://doi.org/10.3390/cancers13051164
Bakhrushina, E. O., Shumkova, M. M., Avdonina, Y. V., Ananian, A. A., Babazadeh, M., Pouya, G., Grikh, V. V., Zubareva, I. M., Kosenkova, S. I., Krasnyuk, I. I., Jr., & Krasnyuk, I. I. (2025). Transdermal drug delivery systems: Methods for enhancing skin permeability and their evaluation. Pharmaceutics, 17(7), 936. https://doi.org/10.3390/pharmaceutics17070936
Barnum, L., Samandari, M., Schmidt, T. A., & Tamayol, A. (2020). Microneedle arrays for the treatment of chronic wounds. Expert Opinion on Drug Delivery, 17(12), 1767–1780. https://doi.org/10.1080/17425247.2020.1819787
Cassano, R., Cuconato, M., Calviello, G., Serini, S., & Trombino, S. (2021). Recent advances in nanotechnology for the treatment of melanoma. Molecules, 26(4), 785. https://doi.org/10.3390/molecules26040785
Chatzilakou, E., Hu, Y., Jiang, N., & Yetisen, A. K. (2024). Biosensors for melanoma skin cancer diagnostics. Biosensors and Bioelectronics, 250, 116045. https://doi.org/10.1016/j.bios.2024.116045
Chen, M., Quan, G., Wen, T., Yang, P., Qin, W., Mai, H., Sun, Y., Lu, C., Pan, X., & Wu, C. (2020). Cold to hot: Binary cooperative microneedle array-amplified photoimmunotherapy for eliciting antitumor immunity and the abscopal effect. ACS Applied Materials & Interfaces, 12(29), 32259–32269. https://doi.org/10.1021/acsami.0c05090
Chong, R. H. E., Gonzalez-Gonzalez, E., Lara, M. F., Speaker, T. J., Contag, C. H., Kaspar, R. L., Coulman, S. A., Hargest, R., & Birchall, J. C. (2013). Gene silencing following siRNA delivery to skin via coated steel microneedles: In vitro and in vivo proof-of-concept. Journal of Controlled Release, 166(3), 211–219. https://doi.org/10.1016/j.jconrel.2012.12.030
Crasta, A., Painginkar, T., Sreedevi, A., Pawar, S. D., Badamane Sathyanarayana, M., Vasantharaju, S. G., Osmani, R. A. M., & Ravi, G. (2025). Transdermal drug delivery system: A comprehensive review of innovative strategies, applications, and regulatory perspectives. OpenNano, 24, 100245. https://doi.org/10.1016/j.onano.2025.100245
Hernández-Domínguez, D. A., Aldaco-Sarvide, F., Cervantes-Sánchez, G., Torrecillas-Torres, L., & Mendoza Balderas, A. (2023). Mortality patterns of melanoma in Mexico over the last 2 decades. Medical Research Archives, 11(2). https://doi.org/10.18103/mra.v11i2.2842
Donnelly, R. F., Singh, T. R. R., Garland, M. J., Migalska, K., Majithiya, R., McCrudden, C. M., Kole, P. L., Mahmood, T. M. T., McCarthy, H. O., & Woolfson, A. D. (2012). Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery. Advanced Functional Materials, 22(23), 4879–4890. https://doi.org/10.1002/adfm.201200864
Duarah, S., Sharma, M., & Wen, J. (2019). Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population. European Journal of Pharmaceutics and Biopharmaceutics, 136, 48–69. https://doi.org/10.1016/j.ejpb.2019.01.005
Huang, S., Liu, H., Huang, S., Fu, T., Xue, W., & Guo, R. (2020). Dextran methacrylate hydrogel microneedles loaded with doxorubicin and trametinib for continuous transdermal administration of melanoma. Carbohydrate Polymers, 246, 116650. https://doi.org/10.1016/j.carbpol.2020.116650
Instituto Nacional de Estadística y Geografía. (2025, 25 de febrero). Estadísticas de defunciones registradas (EDR). INEGI — Estadísticas de defunciones registradas
Jung, J. H., & Jin, S. G. (2021). Microneedle for transdermal drug delivery: Current trends and fabrication. Journal of Pharmaceutical Investigation, 51(5), 503–517. https://doi.org/10.1007/s40005-021-00512-4
Kaur, S. D., Choudhary, S., Sen, S., Pemmaraju, D. B., Singh, S. K., & Kapoor, D. N. (2025). Microneedle patches: The next frontier in cardiovascular care. Drug Delivery and Translational Research, 15(9), 2951–2966. https://doi.org/10.1007/s13346-025-01802-2
Lan, X., Zhu, W., Huang, X., Yu, Y., Xiao, H., Jin, L., Pu, J. J., Xie, X., She, J., Lui, V. W. Y., Chen, H.-J., & Su, Y.-X. (2020). Microneedles loaded with anti-PD-1–cisplatin nanoparticles for synergistic cancer immuno-chemotherapy. Nanoscale, 12(36), 18885–18898. https://doi.org/10.1039/D0NR04213G
Li, J. Y., Feng, Y. H., He, Y. T., Hu, L. F., Liang, L., Zhao, Z. Q., Chen, B. Z., & Guo, X. D. (2022). Thermosensitive hydrogel microneedles for controlled transdermal drug delivery. Acta Biomaterialia, 153, 308–319. https://doi.org/10.1016/j.actbio.2022.08.061
Lin, X., Miao, L., Wang, X., & Tian, H. (2020). Design and evaluation of pH-responsive hydrogel for oral delivery of amifostine and study on its radioprotective effects. Colloids and Surfaces B: Biointerfaces, 195, 111200. https://doi.org/10.1016/j.colsurfb.2020.111200
Liu, J., Hu, A., Yang, Y., Huang, S., Mao, J., Liu, Y., Chen, C., Cheng, Z., & Liu, W. (2023). Recent advances and perspectives of microneedles as transdermal delivery vehicles for analgesic medications. Journal of Drug Delivery Science and Technology, 84, 104518. https://doi.org/10.1016/j.jddst.2023.104518
Lu, Y., Yu, H., Wang, L., Shen, D., & Liu, J. (2023). Preparation of phenylboronic acid-based glucose-responsive hydrogels and microneedles for regulated delivery of insulin. European Polymer Journal, 192, 112061. https://doi.org/10.1016/j.eurpolymj.2023.112061
Luo, X., Yang, L., & Cui, Y. (2023). Microneedles: Materials, fabrication, and biomedical applications. Biomedical Microdevices, 25(3), 20. https://doi.org/10.1007/s10544-023-00658-y
Lyu, S., Dong, Z., Xu, X., Bei, H.-P., Yuen, H.-Y., Cheung, C.-W. J., Wong, M.-S., He, Y., & Zhao, X. (2023). Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration. Bioactive Materials, 27, 303–326. https://doi.org/10.1016/j.bioactmat.2023.04.003
Mantilla Rosa, C., Vancheswaran, A., & Ariyan, C. E. (2024). T-cell immunotherapy for melanoma. Surgical Oncology, 57, 102160. https://doi.org/10.1016/j.suronc.2024.102160
Menon, I., Bagwe, P., Gomes, K. B., Bajaj, L., Gala, R., Uddin, M. N., D’Souza, M. J., & Zughaier, S. M. (2021). Microneedles: A new generation vaccine delivery system. Micromachines, 12(4), 435. https://doi.org/10.3390/mi12040435
Raina, N., Pahwa, R., Thakur, V. K., & Gupta, M. (2022). Polysaccharide-based hydrogels: New insights and futuristic prospects in wound healing. International Journal of Biological Macromolecules, 223, 1586–1603. https://doi.org/10.1016/j.ijbiomac.2022.11.115
Shajari, N., Baradaran, B., Tohidkia, M. R., Nasiri, H., Sepehri, M., Setayesh, S., & Aghebati-Maleki, L. (2024). Advancements in melanoma therapies: From surgery to immunotherapy. Current Treatment Options in Oncology, 25(8), 1073–1088. https://doi.org/10.1007/s11864-024-01239-8
Simeonov, M., Yildirim, I., Tzachev, C. T., & Vassileva, E. (2025). Stimuli-responsive hydrogels of poly(methacrylic acid)/poly(N,N-dimethylacrylamide) interpenetrating polymer networks as drug delivery systems for promethazine hydrochloride. Gels, 11(4), 240. https://doi.org/10.3390/gels11040240
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660
Turner, J. G., White, L. R., Estrela, P., & Leese, H. S. (2021). Hydrogel-forming microneedles: Current advancements and future trends. Macromolecular Bioscience, 21(2), 2000307. https://doi.org/10.1002/mabi.202000307
Vázquez-González, M., & Willner, I. (2020). Stimuli-responsive biomolecule-based hydrogels and their applications. Angewandte Chemie International Edition, 59(36), 15342–15377. https://doi.org/10.1002/anie.201907670
Vegad, U., Patel, M., Khunt, D., Zupančič, O., Chauhan, S., & Paudel, A. (2023). pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery. Frontiers in Bioengineering and Biotechnology, 11, 1270364. https://doi.org/10.3389/fbioe.2023.1270364
Wang, Y., Liu, H., Yang, X., Shi, Z., Li, J., Xue, L., Liu, S., & Lei, Y. (2023). A responsive hydrogel-based microneedle system for minimally invasive glucose monitoring. Smart Materials in Medicine, 4, 69–77. https://doi.org/10.1016/j.smaim.2022.07.006
Wu, C., Yu, Q., Huang, C., Li, F., Zhang, L., & Zhu, D. (2024). Microneedles as transdermal drug delivery system for enhancing skin disease treatment. Acta Pharmaceutica Sinica B, 14(12), 5161–5180. https://doi.org/10.1016/j.apsb.2024.08.013
Xue, Y., Chen, C., Mi, X., Tan, R., Wang, J., Wu, S., Wang, Y., Xiong, R., Chen, M., Tan, W.-Q., & Lu, H. (2024). Transdermal drug delivery system: Current status and clinical application of microneedles. ACS Materials Letters, 6(3), 801–821. https://doi.org/10.1021/acsmaterialslett.3c01317
Yang, G. R., Kim, W., & Jung, J. H. (2024). Sliding microneedle-lateral flow immunoassay strip device for highly sensitive biomarker detection in interstitial fluid. Biosensors and Bioelectronics, 263, 116590. https://doi.org/10.1016/j.bios.2024.116590
Ye, Y., Yu, J., Wang, C., Nguyen, N.-Y., Walker, G. M., Buse, J. B., & Gu, Z. (2016). Microneedles integrated with pancreatic cells and synthetic glucose-signal amplifiers for smart insulin delivery. Advanced Materials, 28(16), 3115–3121. https://doi.org/10.1002/adma.201506025
Yu, J., Wang, J., Zhang, Y., Chen, G., Mao, W., Ye, Y., Kahkoska, A. R., Buse, J. B., Langer, R., & Gu, Z. (2020). Glucose-responsive insulin patch for the regulation of blood glucose in mice and minipigs. Nature Biomedical Engineering, 4(5), 499–506. https://doi.org/10.1038/s41551-019-0508-y
Zhang, Q., Liu, X., & He, J. (2024). Applications and prospects of microneedles in tumor drug delivery. Journal of Materials Chemistry B, 12(14), 3336–3355. https://doi.org/10.1039/D3TB02646A
Zhang, T., Sun, B., Guo, J., Wang, M., Cui, H., Mao, H., Wang, B., & Yan, F. (2020). Active pharmaceutical ingredient poly(ionic liquid)-based microneedles for the treatment of skin acne infection. Acta Biomaterialia, 115, 136–147. https://doi.org/10.1016/j.actbio.2020.08.023
Zhao, J., Gao, N., Xu, J., Zhu, X., Ling, G., & Zhang, P. (2023). Novel strategies in melanoma treatment using silver nanoparticles. Cancer Letters, 561, 216148. https://doi.org/10.1016/j.canlet.2023.216148
Zhao, Z. Q., Liang, L., Hu, L. F., He, Y. T., Jing, L. Y., Liu, Y., Chen, B. Z., & Guo, X. D. (2022). Subcutaneous implantable microneedle system for the treatment of Alzheimer’s disease by delivering donepezil. Biomacromolecules, 23(12), 5330–5339. https://doi.org/10.1021/acs.biomac.2c01155
