Effect of phosphatidylcholine on the percutaneous penetration of drugs through the dorsal skin of guinea pigs in vitro; and analysis of the molecular mechanism, using attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy

Abstract

Phospholipids are effective penetration enhancers for the transdermal delivery of certain co-applied drugs. Standard in vitro skin percutaneous penetration methods using excised guinea pig dorsal skin were employed to characterize the comparison with penetration of a water-insoluble drug, prednisolone (PR), and a water-soluble drug, diclofenac sodium salt (DFS) enhanced by phosphatidylcholine (PC) from soybean. An ATR-FTIR spectroscopy was used to analyze the molecular mechanism of enhancement of the drug penetration, and to measure the lipid fluidity in the stratum corneum (SC) of guinea pig skin caused by PC. The C-H bond stretching absorbance frequency shifts in the SC of guinea pigs induced a higher and a broader absorbance shifts, and a shift was dependent on the PC concentrations. In addition, the percutaneous penetration of PR was dependent on the PC concentration (up to 10% concentration). On the other hand, the percutaneous penetration of DFS was not dependent on the PC concentration. Further, the percutaneous penetration of PR was proportional to the C-H bond stretching absorbance frequency shifts. In contrast, the percutaneous penetration of DFS was not proportional to the C-H bond stretching absorbance frequency shifts. Furthermore, the accumulation of PR in skin was inversely proportional to the C-H bond stretching absorbance frequency shifts (without a plot of the control). The accumulation of DFS in skin was inversely proportional to the C-H bond stretching absorbance frequency shifts (without a plot of the control). The striking parallelism between the enhancement of the percutaneous penetration of PR and the measured SC lipid fluidity shifts caused by PC suggests that the transdermal water-insoluble drug penetration may be ultimately related to the SC lipid structure. On the other hand, the non-parallelism between the enhancement of the percutaneous penetration of DFS and the measured SC lipid fluidity shifts measurement caused by PC suggests that the mechanism of the transdermal water-soluble drug penetration may not be intimately related to the SC lipid structure.