Chitosan-Polylactic Acid Nanoparticles for Oral Delivery of Esomeprazole: Influence of Seafood Waste-Derived Chitosan Source on Formulation and in Vitro Performance

The oral delivery of acid-labile drugs remains challenging due to degradation in the gastric environment and limited intestinal stability. This investigation aimed to evaluate the influence of chitosan source (snail, crab, periwinkle, and commercial) on the formulation characteristics and in vitro behavior of chitosan–polylactic acid (PLA) nanoparticles intended for the oral administration of esomeprazole. Chitosan derived from seafood waste shells was extracted and used for nanoparticle preparation by an emulsion–solvent evaporation method. The nanoparticles were subjected to measurements of particle size distribution, polydispersity index (PDI), encapsulation efficiency, drug–excipient compatibility, and release behavior under simulated gastrointestinal conditions. The nanoparticles exhibited Z-average particle sizes ranging from 14.64 to 97.39 nm, with homogeneity (PDI < 0.30) and encapsulation efficiencies of 70.08 ± 1.56% to 88.34 ± 0.90%. Fourier transform infrared spectroscopy and differential scanning calorimetry confirmed uniform distribution of the drug into the nanoparticle matrix, with no detectable chemical incompatibility. Release studies showed less than 1% drug release in simulated gastric fluid after 2 h, followed by sustained, diffusion-controlled release of approximately 10–25% in simulated intestinal and colonic media, with significant differences among formulations (p < 0.05). Snail-derived nanoparticles exhibited the slowest cumulative release, followed by periwinkle-derived nanoparticles, whereas commercial chitosan and crab-derived nanoparticles exhibited higher cumulative release across the dissolution period. These findings demonstrate that the chitosan source significantly influences nanoparticle properties and drug-release behavior, supporting the use of seafood-derived chitosan as a promising renewable alternative for nanoparticle-based oral drug delivery applications.