Insulin Encapsulation in a Chitosan–Alginate Matrix and In Vitro Release

Background/Objectives: Although insulin therapy has been fundamental in the management of diabetes mellitus since its discovery, limitations associated with conventional administration routes continue to drive the development of alternative delivery strategies. This study reports the design, synthesis, and characterization of a chitosan–alginate nanoparticulate system for the encapsulation and pH-responsive release behavior of recombinant human insulin, developed via ionic crosslinking with sodium tripolyphosphate (TPP). Methods: Nanoparticles were prepared by ionic crosslinking. Physicochemical characterization was carried out by UV–vis spectroscopy, Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR–ATR), dynamic light scattering (DLS), zeta potential analysis, fluorescence spectroscopy, and scanning electron microscopy (SEM). In vitro release studies were conducted at pH 4.5 and 7.4 to simulate physiological environments. Results: The nanoparticles achieved an encapsulation efficiency (EE%) of 30 ± 2.6% and a zeta potential of 41 ± 1.7 mV (pH 4.0). SEM analysis revealed mostly elongated nanoparticles, while DLS measurements confirmed nanometric sizes. The release profile demonstrated rapid insulin release at acidic pH (4.5) and sustained release at slightly basic pH (7.4). After three months of storage at room temperature, the lyophilized nanoparticles allowed continued release at pH 7.4. Conclusions: The synthesized chitosan–alginate nanoparticles provide a biocompatible platform for the encapsulation and release of recombinant human insulin. These findings can contribute to the development of nanosystems as an alternative for insulin delivery, thereby improving therapeutic adherence and accessibility.