Effect of Liposomes on Permeation of Diclofenac Through Cadaver Skin: In-vivo Evaluation Using Animal Models

Abstract

Liposomes interact with the stratum corneum and may be responsible for enhanced transdermal drug penetration. This study was carried out to compare the effect of liposomes on the permeation of diclofenac sodium with the conventionally available non-liposomal diclofenac gel. Preliminary in-vitro studies using fluorescein sodium as a marker showed 1.5- and 1.35- fold increased flux for small unilamellar vesicle and multilamillar vesicle liposome formulations, respectively, compared with non-liposomal fluorescein sodium. This was followed by diclofenac formulations, Lipogel-a (1% w/w diclofenac sodium), Lipogel-b (1.16% w/w diclofenac diethylammonium equiv. 1% w/w diclofenac sodium) and commercially available diclofenac gel. The Lipogel-a and Lipogel-b showed 2- and 1.5-times greater flux compared with conventional non-liposomal diclofenac gel. The pharmaco-kinetic profile in mice was studied as an experimental animal model and the drug concentration in blood was measured at various time points. Lipogel-a, Lipogel-b and conventional diclofenac gel were also compared for their anti-inflammatory activity using carrageenan and Freund's adjuvant models of inflammation. The significant pharmacokinetic profile and enhanced efficacy in pharmacodynamic parameters suggest that liposomes are responsible for enhanced drug penetration. Liposomes enhance drug penetration across the epidermis and thus could be used as alternative carriers to organic and inorganic penetration enhancers.