Chitosan-Derived Nanocarrier Polymers for Drug Delivery and pH-Controlled Release in Type 2 Diabetes Treatment.

Abstract

Diabetes, particularly Type 2 Diabetes Mellitus (T₂DM), is a chronic metabolic disorder with high and increasing global prevalence, characterized by insulin resistance and inadequate insulin secretion. Despite advancements in novel drug delivery systems, widespread and systematic treatment of advanced glycation end products (AGEs) remains challenging due to issues like drug toxicity, low water solubility, and uncontrolled release. Thus, developing nanoplatforms with controlled release capabilities has become a major research focus. Due to its excellent biocompatibility and drug delivery properties, chitosan has attracted considerable attention as a typical biopolymer. In this study, we designed and synthesized an intelligent fluorescence-pH sensitive nanopolymer material using chitosan. We loaded drug 1 and chromium phthalocyanine (CrPc) into folic acid-conjugated carboxymethyl chitosan (FA-CMCS) nanocarriers, forming FA-CMCS@1-CrPc. Comprehensive characterization of FA-CMCS@1-CrPc was conducted using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), and gas adsorption analysis (BET). The results indicate that the nanomaterial was successfully synthesized and exhibits excellent specific surface area, biocompatibility, and fluorescence response. Further research revealed that FA-CMCS@1-CrPc not only achieved controlled drug release but also could regulate drug release by adjusting pH. Additionally, due to its strong fluorescence performance, the nanomaterial demonstrated higher detection sensitivity, especially for monitoring the release of 5% trace drugs. An in vitro model of insulin-resistant cells was established to evaluate the effects of the drug delivery system on glucose degradation and AGE-RAGE regulation, providing a foundation for the development of new T₂DM drugs.