Effects of β-cyclodextrins on skin: implications for the transdermal delivery of piribedil and a novel cognition enhancing-drug, S-9977

The effects of β-cyclodextrin (β-CD), randomly methylated β-cyclodextrin (RAMEB) and 2-hydroxypropyl β-cyclodextrin (HPβ-CD) on skin were investigated. The three cyclodextrins (CDs) were able to destabilize model liposomes and to extract significant amounts of cholesterol from isolated stratum corneum (SC). However, only RAMEB extracted all the major lipid classes from isolated SC, as shown by thin layer chromatography. Both RAMEB and HPβ-CD could release 5–10% of the extractable cholesterol as well as proteins from hairless rat skin. Nevertheless, CDs did not induce any major modification of the differential scanning calorimetry (DSC) profile or the Fourier-transformed infrared (FTIR) spectrum of SC. This was explained by the low percutaneous penetration of CDs. Furthermore, the influence of RAMEB on the transdermal diffusion through hairless rat skin of piribedil, a central dopaminergic agonist and of S-9977, a novel cognition enhancing drug, was studied. RAMEB was found to decrease the transdermal flux of piribedil, with which it forms an inclusion complex, as shown by NMR. Conversely, RAMEB increased by 2-fold the percutaneous absorption of the S-9977 hydrochloride, which does not interact with CD. Finally, a combination of oleic acid and RAMEB greatly increased by about 30-fold the flux of S-9977 hydrochloride.