Tailoring solulan C24 based niosomes for transdermal delivery of donepezil: In vitro characterization, evaluation of pH sensitivity, and microneedle-assisted Ex vivo permeation studies

Abstract

The present investigation aims at encapsulating donepezil (DNP) in a niosomes to avert the side effects and to deliver the intact carrier across the skin barrier by modulating its physicochemical properties. The finding conclusively demonstrated that entrapment efficiency and the alteration in the niosome size are associated with the change in the span 60: cholesterol ratio, sonication, and hydration volume. The addition of 5 mM of solulan C24 to the optimized formulation (NSV5SolC24) formed stable niosomes with a mean particle size of 180.1 ± 1.83 nm and entrapment efficiency of 82.15% ± 1.54%. The cryo-SEM image and in vitro drug release profile revealed that the NSV5SolC24 is pH-sensitive. FTIR spectral analysis of NSV5SolC24 suggested that the ether and ester group in the NSV5SolC24 complex undergoes SN2 cleavage and hydrolysis at lower pH, thus enhancing DNP release. The microneedle (MN)-assisted studies with MN1200 showed a 29-fold increase in transdermal permeation of intact NSV5SolC24 against the passive method in porcine skin. The intact NSV5SolC24 carrying DNP was translocated across the skin barrier successfully at a steady flux rate of 9.89 ± 0.923 μg/cm2/h. Nevertheless, further in vivo studies are recommended to elucidate the pH sensitivity and clinical efficacy of the prepared drug delivery system. © 2020 Elsevier B.V.