Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Study on the efficacy of association and internalization of biopolymeric NPs functionalized with exendin-4 on pancreatic islets(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2022-08-30) Contreras Sánchez, Azazel Monserrat; Lozano García, Omar; emipsanchez; García Rivas, Gerardo de Jesús; Ramón Azcón, Javier; Cholula Díaz, Jorge Luis; School of Medicine and Health Sciences; Campus Monterrey; Alves Figueiredo, Hugo JorgePharmacological treatments of diabetes mellitus have the main purpose of maintaining glucose levels and enhancing metabolism, due that most of the drugs are taken orally, they present limitations in delivery specificity. Thus, there is a necessity to develop novel strategies for drug delivery systems based on nanotechnology. Among these, nanoparticles (NPs), have emerged as a promising candidate to improve the delivery by prolonging drug half-life time, and regulating their kinetics release. Furthermore, incorporating a homing peptide to these NPs increases the interaction with the biological system by promoting target specificity. In this work, we developed and optimized NPs based on PLGA and PEG. These NPs were functionalized with a homing peptide drug for pancreatic islets, exendin-4 (Ex-4). Results from hydrodynamic diameter of NPs-Ex-4 at different molar ratio ranged 199.06 ± 50.10 nm with a negative zeta potential. The yield for Ex-4 functionalization with different molar ratio, 1: 0.5 and 1:1, resulted in 0.57 ± 0.28 % and 12.08 ± 3.20%, respectively. Being the molar ratio 1:1 the best protocol for synthesis. The presence of Ex-4 in the surface of the NPs was confirmed by 𝐻 1𝑁𝑀𝑅 spectra. For In vitro studies, FITC was encapsulated in NPs/NPs-Ex-4 to analyze the association and internalization in pancreatic islets. Results demonstrated that there are statistically significant differences of association of NPs/NPs-Ex-4, with a higher association observed in NPs-Ex-4, resulting in a in 31.6 ± 1.36 % of FITC-positive cells to the total area of the islet. The results suggest NPs can internalize into the islet cells after 24 hrs of administration. On the other hand, NPs-Ex-4 showed an incretin effect on insulin secretion associated with the activation of the receptor GLP-1, which activates PKA signaling pathway. This approach emphasizes the concept of multidrug delivery system with targeting capabilities to target pancreatic islets.