Development of a cationic bionanocomplex from N-aryl-chitosan derivatives for controlled drug release

Drug delivery systems (DDS) often exhibit low solubility, uncontrolled release and adverse side effects. An alternative strategy is the development of bionanocomplexes capable of sustaining the release of active ingredients. In this study, a cationic bionanocomplex was prepared using two aryl-modified chitosan derivatives-arylhydroxy (OHCh) and aryltrimethylammonium (TMACh)-for the controlled release of diclofenac sodium, fluorescein sodium and tetracycline. ¹H NMR analysis confirmed a high degree of substitution for OHCh2 (∼98%) and quaternization for TMACh5 (∼85%). Morphological characterization revealed spherical particles of approximately 200 nm. Their colloidal stability was examined under variations in pH, ionic strength, temperature and time, demonstrating strong environmental sensitivity. Cytotoxicity assays in HCT116 cells indicated high biocompatibility for chitosan and OHCh2 (>85%), moderate effects for TMACh (∼75%), and increased cytotoxicity for the hybrid TMAOHCh (60-65%). The bionanocomplex also showed substantial swelling (∼787% in 2 h). Regarding drug loading, tetracycline presented the highest encapsulation efficiency (69%) and loading content (68 mg g^-1). In contrast, diclofenac exhibited the fastest release (62% in 5 h), followed by fluorescein (20%) and tetracycline (11%). Kinetic modeling indicated non-Fickian diffusion for diclofenac and fluorescein (Korsmeyer-Peppas model), while tetracycline followed Higuchi diffusion. Overall, these findings demonstrate that aryl-modified chitosan bionanocomplexes are promising candidates for sustained and controlled drug delivery applications.