Formulation and evaluation of in-situ forming poloxamer-based hydrogel containing thiolated chitosan nanoparticles as intranasal galantamine delivery system

Intranasal treatment enables circumvention of the blood-brain barrier with direct targeting of cerebral tissues. Here, in situ-forming hydrogel of Poloxamer 407 containing thiolated chitosan nanoparticles (TCS-NPs) was developed for nasal delivery of galantamine. The thiolation value was 198.6 μmol/g. The NPs produced via the desolvation method exhibited a small particle size of around 98 nm and a galantamine entrapment efficiency of about 40 %. TEM image showed spherical NPs around 100 nm. The hydrogel indicated a 96 % release of the drug in 24 h. In the rheological studies, the formulation showed a higher G′ and G′/G" ratio, indicating gel-like behavior suitable for intranasal delivery. The cellular uptake study demonstrated that the TCS-NPs and galantamine-loaded TCS-NPs were successfully internalized by A172 cells. The bioassays (MTT, DAPI staining, and live/dead) were performed on the A172 and Caco-2 cell lines and revealed the desired biocompatibility of the developed nanoformulation. Ex vivo testing indicated low levels of tissue damage and proved the higher mucoadhesive strength and mucosal retention time of TCS-NPs/poloxamer gel compared to CS-NPs/poloxamer gel. Considering the obtained results, the developed TCS-NPs/poloxamer hydrogel could be a promising delivery system for targeting drugs toward the brain via a minimally invasive approach.