The role of chitosan in modulating physicochemical and biological behavior of solid lipid nanoparticles

Chitosan, a cationic polysaccharide known for its peculiar properties, plays a key role in enhancing biological interactions at mucosal surfaces. This study investigated the role and impact of chitosan on physicochemical and biological properties of Cyclosporine A -loaded solid lipid nanoparticles (SLN). Three types of SLN were developed: SLN devoid of chitosan, chitosan-associated SLN during hot homogenization (CH-SLN), and chitosan-coated SLN (CH-c-SLN). Physicochemical characterization revealed differences in particle shape, with chitosan presence increasing particle size and zeta potential. SAXS/WAXS and DSC studies demonstrated that Cyclosporine A and chitosan influenced lipid organization and thermal behavior. Moreover, mucoadhesion and mucin interaction were stronger in chitosan-associated SLN (CH-SLN), as evidenced by SAXS and ITC, due to chitosan cationic nature. At last, preclinical studies revealed enhanced cellular uptake in presence of chitosan. These findings demonstrated that chitosan-associated SLN enhanced mucoadhesion and cellular interaction while maintaining structural integrity, providing a promising platform for drug delivery.