Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

Omar Rodrigo Guadarrama-Escobar,Pablo Serrano-Castañeda,Clara Luisa Domínguez-Delgado,Adalí Yisell Sánchez-Padrón,Abraham Méndez-Albores,Ericka Anguiano-Almazán,José Juan Escobar-Chávez,Crisóforo Mercado-Márquez,Isabel Marlen Rodríguez-Cruz,German Alberto Chamorro-Cevallos,Betsabé Rodríguez-Pérez,Ivonne Sánchez-Vázquez,Ma Concepción Peña-Juárez

doi:10.3390/pharmaceutics13122023

Abstract

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

Highlights

Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia that is accompanied, to a greater or lesser extent, by the alterations in carbohydrate metabolism
Polymeric nanoparticles loaded with glibenclamide were designed and characteriz
Polymeric nanoparticles loaded with glibenclamide were designed and characterized using the solvent evaporation method

Summary

Introduction

Diabetes mellitus (DM) is a metabolic disorder characterized by the presence of chronic hyperglycemia that is accompanied, to a greater or lesser extent, by the alterations in carbohydrate metabolism. Type 2 diabetes mellitus (DM2) is considered one of the non-communicable chronic diseases with the greatest impact on the quality of life of the world population and constitutes a real health problem. It belongs to the group of diseases that, due to their multiorgan complications, produces physical disability, with a considerable increase in recent years in morbidity and mortality regardless of social, cultural, and economic circumstances [2]. Glibenclamide is a potential second-generation oral sulfonylurea agent that promotes insulin release to keep glucose levels in check. For this reason, it is widely used for the treatment of non-insulin dependent diabetes mellitus. The mechanism of action of glibenclamide seems to be initiated by the linkage of drug molecules with surface receptor in the beta cells’ surface and subsequent reduction in conductance of ATP-sensitive K+ channels [3,4,5,6]

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