Michael D. Garrison

Effect of oleic acid on human epidermis: Fluorescence spectroscopic investigation

The effect of oleic acid on the human epidermis was studied using phase-modulated fluorescence spectroscopy. Fluorescence lifetime and limiting anisotropy of a membrane fluorophore 1,6-diphenyl-1,3,5-hexatriene were measured in human epidermis treated with donor formulations containing 0–5% oleic acid. Transport of benzoic acid across human epidermis was also measured under these conditions. The flux enhancement, changes in the spectral parameters, and uptake of oleic acid into epidermis showed a saturation effect with increasing OA concentration in the formulation. There was a strong correlation between the flux enhancement and the fluorescence lifetime and limiting anisotropy. The present study demonstrates the use of fluorescence spectroscopy to follow the effect of a chemical perturbant on skin structure.

Effect of PGML Excipient Mixture in a Transdermal System on the in Vitro Transport of Estradiol Across Skin

AbstractPurpose. To measure the effect of a combination of excipients from a silicone based pressure sensitive adhesive (PSA) on drug transport across skin. Methods. Partitioning of propylene glycol monolaurate (PG-ML) from silicone PSA and a solution formulation into the stratum corneum (SC) was measured using radiolabeled PG-ML. Transport of a model drug, estradiol, as well as PG-ML across skin were measured in vitro using heat separated epidermis from human cadaver skin. Results. The PG-ML partitioning into SC showed a saturation and was independent of the formulation. The local dielectric of the lipid bilayers of the SC showed an increase as a result of PG-ML uptake, as determined by the decrease in fluorescence lifetime of a lipophilic probe incorporated into the SC. However, there was no alteration of lipid packing in SC. Conclusions. The PG-ML and estradiol transport showed a good correlation over 3 days, suggesting that the two species are co-transported across the epidermis.

Frequency-domain fluorescence spectroscopy of human stratum corneum

The intercellular lipid lamellae of mammalian stratum corneum (SC) constitute the major barrier to percutaneous penetration of drugs and other solute molecules. In order to understand the barrier property of skin on a molecular level, we have initiated fluorescence spectroscopic investigation of the membranous structures of the SC and related model systems using the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Incorporated into distearoylphosphatidylcholine and stratum corneum bilayers, DPH fluorescence reflected the change in lipid structure under thermal and chemical perturbations. Using a multiharmonic frequency approach, we measured the fluorescence lifetime and rotational correlation times for DPH in these systems. Our data indicated that a biexponential decay ((tau) 1 approximately equals 9 ns, (tau) 2 approximately equals 1.5 ns) described the intensity decay, while a hindered rotor model ((phi) approximately equals 5 ns, r(infinity ) approximately equals 0.3) described the anisotropy decay. These parameters reported the known thermotropic phase transition in porcine stratum corneum, and the influence of the penetration enhancer oleic acid in human epidermis. Thus, we have shown frequency- domain fluorescence spectroscopy to be a facile and powerful tool for monitoring the permeability of a solid tissue such as the SC.