Phospholipids affect stratum corneum lipid bilayer fluidity and drug partitioning into the bilayers

Phospholipids, e.g. fluid-state EPC (L-alpha-phosphatidylcholine from egg y olk), may diffuse into the stratum corneum and enhance dermal and transderm al drug penetration, while many other phospholipids, e.g. gel-state DSPC (d istearoylphosphatidyl choline), are not able to do this. These effects are suggested to be due to the interactions between the phospholipids and the s kin lipid bilayers, and so an in vitro method was developed to evaluate the influence of phospholipids on the distribution of drugs to stratum corneum lipids. The distribution coefficients of estradiol, progesterone and propr anolol between stratum corneum lipid liposomes (SCLLs) without phospholipid s or with EPC, DSPC, SPC (L-alpha-phosphatidylcholine from soybean) or DOPE (dioleylphosphatidyl ethanolamine), and pH 7.4 buffer were determined. Flu id-state phospholipids in SCLLs increased the partitioning of drugs into SC LLs, while gel-state lipid, DSPC, did not. The increased distribution of dr ugs into the SCLLs was at least partially due to the increased fluidity of SCLL bilayers by phospholipids, which was shown using steady-state fluoresc ence anisotropy. This in vitro method enables screening of the effects of p hospholipids and other permeation enhancers on stratum corneum bilayer flui dity and drug partitioning. (C) 1999 Elsevier Science B.V. All rights reser ved.