Intranasal administration of berberine-loaded hydrogel ameliorates okadaic acid-induced cognitive deficit in mice

A chemical crosslinked hydrogel was formed due to interaction between -CHO groups present in aldehydemodified xanthan gum and amine-terminated poloxamer, named as HXGP. The formation of fabricated crosslinking hydrogel was confirmed by the presence of a peak at 1635 cm(-1), in the FTIR spectra indicating the formation of -C = N- bond between gum and amine-terminated poloxamer. Also, the rheology analysis showed the formation of hydrogel i.e., storage modulus (G') > loss modulus (G ''). Also, an upsurge in linear viscoelastic range was increased from 0.264 % to 0.558 %, and flow points (3.85 to 83.34) while increasing the ratio of amine-terminated poloxamer during the fabrication of hydrogels. Also, in vitro cytotoxicity using MTT assay showed >80 % cell viability. Moreover, the ex vivo nasal cytotoxicity study confirmed the biocompatibility of HXGP. The plasma pharmacokinetic parameters were improved i.e., similar to 2.57 times increased Cmax after intranasal administration of berberine chloride (BBC)-loaded hydrogel. Moreover, a significant amount of berberine in the brain was found to be present in hydrogel-treated group than naive BBC. Also, the IVIS (R) showed the feasibility of hydrogel for nose-to-brain delivery up to 24 hrs. The neurobehavioral studies confirmed the highly significant rescue of cognitive deficit in okadaic acid-induced AD mice model after the administration of BBC-loaded HXGP (BBC-HXGP). Also, enzyme-linked immunosorbent assay (ELISA) confirmed the significant reduction (***p < 0.001) in phosphorylated tau protein in HXGP treatment in comparison with BBC treatment (*p < 0.05) in okadaic acid-treated groups.