Chitosan-lysine nanoparticles for sustained delivery of capecitabine: Formulation, characterization, and evaluation of anticancer and antifungal properties with molecular docking insights on anti-inflammatory potential

This study aimed to develop and evaluate chitosan/lysine nanoparticles as a delivery system for capecitabine in cancer treatment. Nanoparticles were synthesized via ionic gelation and characterized using FTIR, XRD, SEM, TEM, and UV spectroscopy. FTIR analysis confirmed successful drug loading, while XRD revealed the amorphous nature of the encapsulated drug. TEM imaging showed particle sizes ranging from 40-60 nm, ideal for tumor penetration. The formulation achieved a high drug entrapment efficiency of 98 %, indicating strong drugpolymer interaction. Sustained drug release was observed in PBS at pH 7.4 with the Higuchi model showing the best fit (R2 = 0.99), indicating a diffusion-controlled release mechanism. Biodegradation assays using lysozyme confirmed the nanoparticles ' biocompatibility. The formulations exhibited superior antioxidant potential, with antioxidant activity of capecitabine-loaded nanoparticles showing a 35 % increase compared to the control. Antimicrobial tests showed efficacy against Mucor, Aspergillus, B. cereus, and E. coli, with inhibition zones ranging from 10-22 mm. Molecular docking analysis using the GRAMM server explored interactions of chitosan/lysine nanoparticles and capecitabine-loaded nanoparticles with human neutrophil elastase (HNE) 1H1B protein, showing favorable binding energies of-6.2 kcal/mol and-7.1 kcal/mol, respectively, suggesting potential anti-inflammatory properties. This research underscores the potential of chitosan-lysine nanoparticles as effective carriers for capecitabine, offering controlled drug release and improved therapeutic outcomes in cancer treatment, while also highlighting their potential in anti-inflammatory applications.