Studies on the skin penetration mechanisms of liposomal formulations

Liposomes have also been shown to enhance the penetration of a variety of drugs in the skin. When drug substances are applied on the skin in solution form, drug penetration mainly depends on the physicochemical properties of the drug however, incorporation of drugs in the liposomes results in a rather complex interaction between the stratum corneum, phospholipid membrane and drug. Studies in this thesis were designed to probe the interactions between the stratum corneum and invasomes in order to gain a better understanding of the mechanisms involved in the drug delivery to skin from invasomes. Confocal Raman microscopy was employed to study the co-diffusion of liposomally entrapped drugs and the phospholipids forming the liposomal bilayers. The study was based on a premise that if diffusion patterns of both, drug and phospholipid could be studied in the skin then it might allow us to comment on the underlying mechanism responsible for penetration of drug as each mechanism should give rise to a different diffusion profile. A method was developed to obtain non-invasive Raman depth profiles in ex vivo human skin. Optical biopsies of untreated skin were measured along with diffusion profiles of skin treated with beta-carotene and deuterated water. Tip-enhanced Raman scattering (TERS) was the tool of choice as TERS is not limited by the Abbe’s resolution limit and is an excellent tool for providing chemical and structural information. Conventional tape stripping technique was adopted to allow application of TERS. In vivo human skin was treated with deuterated invasomes and the stratum corneum was progressively removed. TERS and atomic force microscopy measurements revealed that intact invasome vesicles did penetrate the stratum corneum. For the first time spectroscopic evidence along with high resolution imaging confirmed that intact liposomes can penetrate the human stratum corneum.