Composite chitosan-transfersomal vesicles for improved transnasal permeation and bioavailability of verapamil

Abstract

The creation of composite systems has become an emerging field in drug delivery. Chitosan has demonstrated several pharmaceutical advantages, especially in intranasal delivery. In this manuscript, a comparative study was conducted between regular vesicles (transfersomes and penetration enhancer vesicles) and composite vesicles (chitosan containing transfersomes and penetration enhancer vesicles) loaded with a model antihypertensive drug; verapamil hydrochloride VRP. Composite vesicles displayed larger particle size than regular vesicles owing to the coating potential of chitosan on the vesicular bilayer as displayed by transmission electron microscopy, with an increased viscosity of composite vesicles and a shift in the zeta potential values from negative to positive. The entrapment efficiency of VRP in the vesicles ranged from 24 to 64%, with best physical stability displayed with transfersomal vesicles prepared using sodium deoxycholate. Chitosan slowed the in vitro release of VRP from the selected formulation but managed to achieve high penetrability across sheep nasal mucosa as displayed by confocal laser microscopy. The chitosan composite transfersomal formulation exhibited absolute bioavailability of 81.83% compared to the oral solution which displayed only 13.04%. Findings of this manuscript highly recommend chitosan as a promising functional additive in vesicular formulations to improve the intranasal delivery of drugs with low oral bioavailability.