Preparation and Characterization of HP-β-Cyclodextrin-Integrated Chitosan Nanoparticles for Non-invasive Insulin Delivery

Abstract

Background: Diabetes affects over 537 million adults globally, with insulin therapy remaining essential — particularly for type 1 diabetes. However, the oral delivery of insulin is hindered by poor bioavailability due to enzymatic degradation, low permeability, and mucosal barriers. Objectives: The main goal of this project was to design and evaluate a nanocarrier made of chitosan (CS) incorporated with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the delivery of insulin. Methods: The composite was prepared by the ionic gelation of CS with sodium tripolyphosphate (TPP) as a crosslinker. Results: The optimized nanocarrier (0.2% CS, 1.5 mg/mL TPP, six mM HP-β-CD) exhibited a particle size of 62.5 nm. The insulin complexation with HP-β-CD facilitates insulin entrapment over the nanoparticle (NP) surface. The inclusion complex was analyzed in solution through phase solubility diagrams. The stability constant was calculated at different temperatures (10, 25, and 37°C; pH = 4.6) to determine the thermodynamic parameters of inclusion. The release profile showed insulin was released rapidly (70% insulin in 20 min). Conclusions: The engineered TPP/HP-β-CD/CS nanocarrier demonstrates high efficiency in encapsulating insulin, enhances its solubility and stability, and enables rapid release, making it a promising candidate for oral or nasal delivery of macromolecular drugs.