An EPR spin probe study of the interactions between PC liposomes and stratum corneum membranes

Abstract

The electron paramagnetic resonance (EPR) spin labeling methodology was used to analyze the interactions of phosphatidylcholine (PC) liposomal formulations that are commonly used as transepidermal drug delivery systems with stratum corneum (SC) membranes. The lipid dynamics of five liposome formulations were evaluated to study the influences of sorbitan monooleate (Span80), cholesterol, and cholesterol with the charged lipids 2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG) on the molecular dynamics of PC vesicles. The EPR spectra of 5-doxyl-stearic acid (5-DSA) showed that the addition of Span80 to the liposomes increased the lipid fluidity, whereas cholesterol had the opposite effect, and the combination of charged lipids and cholesterol did not additionally influence the lipid bilayer dynamics. Fatty acid spin-labeled SC membranes were treated with the liposome formulations, leading to migration of the spin label to the molecular environment of the formulation and the presence of two spectral components representing distinct mobility states. In terms of molecular dynamics, these environments correspond to the lipid domains of the untreated SC and the liposome, indicating a poor interaction between the liposome and SC membranes. However, the contact was sufficient to allow a pronounced exchange of the spin-labeled fatty acid. Our data suggest that flexible liposomes may access the inner intercellular membranes of the SC and facilitate mutual lipid exchange without losing their relative liposomal integrity.

Keywords: EPR; Flexible liposomes; Spin labels; Transepidermal drug delivery.