Tm. Suhonen et al., TRANSEPIDERMAL DELIVERY OF BETA-BLOCKING-AGENTS - EVALUATION OF ENHANCER EFFECTS USING STRATUM-CORNEUM LIPID LIPOSOMES, Journal of controlled release, 43(2-3), 1997, pp. 251-259
The effect of the penetration enhancers Atone, 1-dodecanol, and dodecy
l-2-(N,N-dimethylamino)propionate (DDAIP) on the structural integrity
of liposomes composed of stratum corneum (SC) lipids was studied. With
increasing enhancer concentration (0-1.5 mM) in the incubation medium
(30% w/w aqueous ethanol), the lipid bilayer structure was found to b
ecome more disordered, as demonstrated by a decrease in 1,6-diphenyl-1
,3,5-hexatriene (DPH) fluorescence anisotropy, and the efflux of the e
ntrapped hydrophilic fluorescent marker, calcein, was found to increas
e. The lipid fluidizing effects of Atone and DDAIP were stronger than
that of 1-dodecanol. In addition, transport of propranolol hydrochlori
de and sotalol hydrochloride, administered as solutions in 45% w/w aqu
eous ethanol containing 0-10 mM enhancer, was investigated across huma
n epidermis in vitro. The flux enhancements of Atone and DDAIP were mo
re pronounced with the hydrophilic sotalol and increased with increasi
ng enhancer concentration, whereas 1-dodecanol was found to have a neg
ligible effect. The flux of the lipophilic propranolol, on the other h
and, was only slightly augmented by the enhancers. The lipid disorderi
ng effects and flux enhancement (especially that of the hydrophilic dr
ug) followed a similar trend demonstrating the importance of SC lipid
interactions as a mode of action of the enhancers studied.