EFFECTS OF BETA-CYCLODEXTRINS ON SKIN - IMPLICATIONS FOR THE TRANSDERMAL DELIVERY OF PIRIBEDIL AND A NOVEL COGNITION ENHANCING-DRUG, S-9977

The effects of beta-cyclodextrin (beta-CD), randomly methylated beta-c yclodextrin (RAMEB) and 2-hydroxypropyl beta-cyclodextrin (HP beta-CD) on skin were investigated. The three cyclodextrins (CDs) were able to destabilize model liposomes and to extract significant amounts of cho lesterol from isolated stratum corneum (SC). However, only RAMEB extra cted all the major lipid classes from isolated SC, as shown by thin la yer chromatography. Both RAMEB and HP beta-CD could release 5-10% of t he extractable cholesterol as well as proteins from hairless rat skin. Nevertheless, CDs did not induce anp major modification of the differ ential scanning calorimetry (DSC) profile or the Fourier-transformed i nfrared (FTIR) spectrum of SC. This was explained by the low percutane ous penetration of CDs. Furthermore, the influence of RAMEB on the tra nsdermal diffusion through hairless rat skin of piribedil, a central d opaminergic agonist and of S-9977, a novel cognition enhancing drug, w as studied. RAMEB was found to decrease the transdermal flux of piribe dil, with which it forms an inclusion complex, as shown by NMR. Conver sely, RAMEB increased by 2-fold the percutaneous absorption of the S-9 977 hydrochloride, which does not interact with CD. Finally, a combina tion of oleic acid and RAMEB greatly increased by about 30-fold the fl ux of S-9977 hydrochloride.