Surface-modified liposomal in-situ nasal gel enhances brain targeting of berberine hydrochloride for Alzheimer's therapy: optimization and in vivo studies.

Abstract

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing in-situ nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3² full-factorial design. Size, morphology, zeta potential, ex-vivo permeation, and in-vitro release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in in-situ gel using poloxamer and Carbopol 934P. Liposomal in-situ gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). In-vivo pharmacokinetic examination of payload from liposomal in-situ gel displayed higher concentration in brain (C_max of 93.50 ng/mL). The liposomal in-situ nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded in-situ gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.