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 aldehyde-modified xanthan gum and amine-terminated poloxamer, named as HXGP. The formation of fabricated cross-linking 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., ∼2.57 times increased C_max 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 naïve BBC. Also, the IVIS® 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.