Evaluación in vivo del efecto terapéutico de nanopartículas cargadas con insulina en un modelo experimental en ratas Wistar

In vivo evaluation of the therapeutic effect of insulin-loaded nanoparticles in an experimental model in Wistar rats

Contenido principal del artículo

Juan Isaac Chávez Corona
Andrea Gisela Tinajero Lozada
Angel Daniel Miguel Ortiz
Sheila Irais Peña Corona
Gerardo Leyva Gómez
María Josefa Bernad Bernad
Carolina Flores Ávila
David Quintanar Guerrero

Resumen

El desarrollo de sistemas de liberación controlada basados en nanopartículas poliméricas constituye una estrategia clave para la administración de compuestos de interés farmacéutico, como la insulina. El quitosano, un polímero derivado de la quitina, por su biocompatibilidad y versatilidad, representa una plataforma prometedora; sin embargo, los métodos tradicionales de síntesis generan una alta dispersión en las propiedades fisicoquímicas, lo que limita su aplicación terapéutica. En este estudio se prepararon nanopartículas de quitosano de bajo peso molecular mediante modificaciones al método de gelación iónica, para el cual se utilizó como agente entrecruzante el tripolifosfato de sodio (TPP) y Eudragit ® L100-55 como recubrimiento entérico, con la finalidad de optimizar su desempeño y la entrega de insulina humana recombinante vía oral. Las nanopartículas presentaron un tamaño promedio de 299,86±21,33 nm, un índice de polidispersión (PDI) de 0,28 ± 0,05 y un potencial zeta de -24,93±1,10 mV, con morfología ovoide uniforme, confirmada por TEM. Se evidenció que el sistema tuvo una disminución importante en los niveles de glucosa sérica en un ensayo piloto in vivo en ratas Wistar.


Palabras clave

Detalles del artículo

Referencias (VER)

CNQFB. (2002). Guía de validación de métodos analíticos.

Cai, H., et al. (2024). Development of a pH-sensitive nanoparticle via self-assembly of fucoidan and protamine for the oral delivery of insulin. Pharmaceutics, 16(10), 1323. https://doi.org/10.3390/PHARMACEUTICS16101323

Cloete, L. (2022). Diabetes mellitus: An overview of the types, symptoms, complications and management. Nursing Standard, 37(1), 61–66. https://doi.org/10.7748/NS.2021.E11709

Datos y cifras sobre la diabetes. (s. f.). Federación Internacional de Diabetes. Recuperado el 24 de agosto de 2025, de https://idf.org/es/about-diabetes/diabetes-facts-figures/

Edo, G. I., Yousif, E., & Al-Mashhadani, M. H. (2024). Chitosan: An overview of biological activities, derivatives, properties, and current advancements in biomedical applications. Carbohydrate Research, 542. https://doi.org/10.1016/j.carres.2024.109199

European Medicines Agency. (s. f.). ICH Q2(R2) Validation of analytical procedures - Scientific guideline. Recuperado el 24 de agosto de 2025, de https://www.ema.europa.eu/en/ich-q2r2-validation-analytical-procedures-scientific-guideline

European Medicines Agency. (s. f.). ICH Q2(R2) Validation of analytical procedures - Scientific guideline. Recuperado el 26 de agosto de 2025, de https://www.ema.europa.eu/en/ich-q2r2-validation-analytical-procedures-scientific-guideline

Faghmous, N., Bouzid, D., Boumaza, M., Touati, A., & Boyron, O. (2021). Optimization of chitosan-coated W/O/W multiple emulsion stabilized with Span 80 and Tween 80 using Box-Behnken design. Journal of Dispersion Science and Technology, 42(10), 1566–1578. https://doi.org/10.1080/01932691.2020.1774387

Fathalla, Z., Al Fatease, A., & Abdelkader, H. (2023). Formulation and in-vitro/ex-vivo characterization of pregelled hybrid alginate-chitosan microparticles for ocular delivery of ketorolac tromethamine. Polymers, 15(13), 2773. https://doi.org/10.3390/POLYM15132773

Gadziński, P., et al. (2022). Ionotropic gelation and chemical crosslinking as methods for fabrication of modified-release gellan gum-based drug delivery systems. Pharmaceutics, 15(1), 108. https://doi.org/10.3390/PHARMACEUTICS15010108

Gutiérrez-Ruíz, S. C., et al. (2024). Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes. Journal of Biological Engineering, 18(1), 1–16. https://doi.org/10.1186/S13036-024-00403-W

Guadarrama-Escobar, O. R., et al. (2023). Chitosan nanoparticles as oral drug carriers. International Journal of Molecular Sciences, 24(5). https://doi.org/10.3390/IJMS24054289

Hemanth, G., Patil, A., Hariprasad, M. G., Moqbel Redhwan, M. A., & Guha, S. (2025). Development, optimization, and characterization of Eudragit-based nanoparticles for Dasatinib delivery. Journal of Biomaterials Science, Polymer Edition, 36(6), 756–778. https://doi.org/10.1080/09205063.2024.2427489

Ikegami, H., Hiromine, Y., & Noso, S. (2022). Insulin-dependent diabetes mellitus in older adults: Current status and future prospects. Geriatrics & Gerontology International, 22(8), 549–553. https://doi.org/10.1111/GGI.14414

Islam, M. A., Barua, S., & Barua, D. (2017). A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles. BMC Systems Biology, 11(1). https://doi.org/10.1186/S12918-017-0491-4

Jain, D., Majumdar, D. K., & Panda, A. K. (2006). Insulin loaded eudragit L100 microspheres for oral delivery: Preliminary in vitro studies. Journal of Biomaterials Applications, 21(2), 195–211. https://doi.org/10.1177/0885328206060436

Jafernik, K., et al. (2023). Chitosan-based nanoparticles as effective drug delivery systems—a review. Molecules, 28(4). https://doi.org/10.3390/MOLECULES28041963

Jelvehgari, M., et al. (2010). Development of pH-sensitive insulin nanoparticles using Eudragit L100-55 and chitosan with different molecular weights. AAPS PharmSciTech, 11(3), 1237–1242. https://doi.org/10.1208/S12249-010-9488-7

Kheiripour, N., et al. (2020). The effects of synthetic orally administrated insulin nanoparticles in comparison to injectable insulin on the renal function markers of type 1-diabetic rats. Iranian Journal of Basic Medical Sciences, 23(6), 810. https://pubmed.ncbi.nlm.nih.gov/32695298/

Koroleva, M. Y., et al. (2018). Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue. IOP Conference Series: Materials Science and Engineering, 311(1), 012024. https://doi.org/10.1088/1757-899X/311/1/012024

Liu, T., Li, J., Tang, Q., Qiu, P., Gou, D., & Zhao, J. (2022). Chitosan-based materials: An overview of potential applications in food packaging. Foods, 11(10). https://doi.org/10.3390/FOODS11101490

Low, C. Y., et al. (2025). Critical updates on oral insulin drug delivery systems for type 2 diabetes mellitus. Journal of Nanobiotechnology, 23(1), 1–25. https://doi.org/10.1186/S12951-024-03062-7

Maurya, R., Ramteke, S., Guru, P., & Jain, N. K. (2022). Oral glucose-responsive nanocarrier system for management of diabetes. Journal of Endocrinology and Metabolism, 12(4-5), 146–160. https://jofem.org/index.php/jofem/article/view/747/284284591

Moore, T. L., et al. (2015). Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chemical Society Reviews, 44(17), 6287–6305. https://doi.org/10.1039/C4CS00487F

Pedroso-Santana, S., & Fleitas-Salazar, N. (2020). Ionotropic gelation method in the synthesis of nanoparticles/microparticles for biomedical purposes. Polymer International, 69(5), 443–447. https://doi.org/10.1002/PI.5970

Purohit, G., & Rawat, D. S. (2022). Characterization techniques for chitosan and its based nanocomposites. In Chitosan-Based Nanocomposite Materials: Fabrication, Characterization and Biomedical Applications (pp. 79–101). https://doi.org/10.1007/978-981-19-5338-5_3

Rezazadeh, M., Safaran, R., Minaiyan, M., & Mostafavi, A. (2021). Preparation and characterization of Eudragit L 100-55/chitosan enteric nanoparticles containing omeprazole using general factorial design: In vitro/in vivo study. Research in Pharmaceutical Sciences, 16(4), 358–369. https://doi.org/10.4103/1735-5362.319574

Romero-Carmona, C. E., et al. (2024). Nanoparticle and microparticle-based systems for enhanced oral insulin delivery: A systematic review and meta-analysis. Journal of Nanobiotechnology, 22(1), 802. https://doi.org/10.1186/s12951-024-03045-8

Sari, D. P., Utami, T. S., Arbianti, R., & Hermansyah, H. (2018). The effect of centrifugation speed and Chitosan-Sodium Tripolyphosphate ratio toward the nanoencapsulation of Sambiloto (Andrographis paniculata) for the formulation of Hepatitis B drug. IOP Conference Series: Earth and Environmental Science, 105(1), 012112. https://doi.org/10.1088/1755-1315/105/1/012112

Seyam, S., Nordin, N. A., & Alfatama, M. (2020). Recent progress of chitosan and chitosan derivatives-based nanoparticles: Pharmaceutical perspectives of oral insulin delivery. Pharmaceuticals, 13(10), 1–29. https://doi.org/10.3390/PH13100307

Van Bavel, N., Issler, T., Pang, L., Anikovskiy, M., & Prenner, E. J. (2023). A simple method for synthesis of chitosan nanoparticles with ionic gelation and homogenization. Molecules, 28(11), 4328. https://doi.org/10.3390/MOLECULES28114328

Wu, Z. M., et al. (2012). Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery. Nanoscale Research Letters, 7(1), 1–8. https://doi.org/10.1186/1556-276X-7-299

Xiao, Y., et al. (2021). Glucose-responsive oral insulin delivery platform for one treatment a day in diabetes. Matter, 4(10), 3269–3285. https://doi.org/10.1016/J.MATT.2021.08.011

Xu, B., Zhang, W., Chen, Y., Xu, Y., Wang, B., & Zong, L. (2018). Eudragit® L100-coated mannosylated chitosan nanoparticles for oral protein vaccine delivery. International Journal of Biological Macromolecules, 113, 534–542. https://doi.org/10.1016/J.IJBIOMAC.2018.02.016

Descargas

Los datos de descargas todavía no están disponibles.

Datos de publicación

Metric
Este artículo
Revisores/as por pares 
0
2.4
Días para la publicación 
376
145

Perfil evaluadores/as  N/D

Declaraciones de autoría

Declaraciones de autoría
Este artículo
Otros artículos
Disponibilidad de datos 
N/D
16%
Financiación externa 
No
32%
Conflictos de intereses 
N/D
11%
Metric
Esta revista
Otras revistas
Artículos aceptados 
0%
33%

Indexado en

Editor y equipo editorial
Perfiles
Sociedad académica 
Universidad Ean
Editorial 
Universidad Ean

Citaciones

Crossref

Scopus
Europe PMC