Gelatin-Incorporated Chitosan-TPP Nanocomposites Enhanced Cumulative and Sustained Bovine Serum Albumin Release

An effective nanocarrier for therapeutic proteins is essential for tissue engineering and regenerative medicine. However, challenges such as nontargeted profile, rapid degradation, burst release, and cytotoxicity limit the efficacy of the potential delivery system. This research aims to design and evaluate bovine serum albumin (BSA)-loaded chitosan/gelatin cross-linked with sodium tripolyphosphate (TPP), enhancing the drug release profile and biocompatibility for potential pharmaceutical applications. In this study, chitosan, a cationic polysaccharide, and gelatin are cross-linked as a nanofiller dispersed in a polymer matrix. TPP can be used to enhance the encapsulation of the BSA molecules. This formulation is designed to offer controlled release properties and improved stability for protein-based drug delivery applications. The physicochemical properties of nanoparticles, including particle size, morphology, encapsulation efficiency, and cumulative release rate, were characterized by using dynamic light scattering, scanning electron microscopy, Fourier transform infrared spectroscopy, and UV-vis spectrophotometry. The conformation of chitosan/gelatin-TPP nanocomposites at pH 3 tended to form with an average size of 6.1 ± 1.1 nm and a moderate polydispersity of 0.328, whereas at pH 5, a broad range of size distribution was formed. A maximum BSA loading of 83.33% was achieved at a chitosan concentration of 0.01% and a TPP concentration of 0.45%. The release kinetics of BSA from chitosan/gelatin-TPP nanocomposites demonstrated that the cumulative and sustained release of BSA was significantly increased within 120 h with increasing gelatin concentrations. Moreover, the cytotoxicity and biocompatibility were assessed using NIH-3T3 fibroblasts, confirming high cell viability after 72 h of incubation. The system showed minimal cytotoxicity, confirming its suitability for therapeutic applications. In addition, the properties of chitosan, gelatin, and TPP are excellent stability, biodegradability, and biocompatibility, which could be further explored for the delivery of other therapeutic agents, providing a way to develop advanced drug delivery technology in regenerative medicine.