Potential use of ascorbic acid-based surfactants as skin penetration enhancers

6-O-Ascorbic acid alkanoates (ASCn) are amphiphilic mols. having phys.-chem. properties that depend on the alkyl chain length. The derivs. of low mol. wt. (n < 11) have enough aq. soly. to produce self-assemblies at room temp. (≈25°C), while those with longer alkyl chains possess a crit. micellar temp. (CMT) higher than 30°C. At higher temps. (T > CMT), ASCn aq. suspensions turn into either micellar solns. or gel phases, depending on the length of the hydrophobic chain. On cooling, coagels are produced, which possess a lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence. The semisolid consistency of such coagels is an interesting property to formulate dermatol. pharmaceutical dosage forms able to solubilize and stabilize different drugs. The objective of the present study was the evaluation of the enhancing permeation effect of ASCn with different chain lengths and to correlate permeability changes with histol. effects. With this purpose, ASCn coagels contg. anthralin (antipsoriasic drug) or fluorescein isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat skin (ex vivo) and mice skin (in vivo), resp. Also, histol. studies were performed aimed at detecting some possible side effects of ASCn. No inflammatory cellular response was obsd. in the skin when ASCn coagels were applied, suggesting non-irritating properties. Light microscopy indicated slight disruption and fragmentation of stratum corneum. The penetration of ASCn through rat skin epidermis was very fast and quant. significant. The permeation of anthralin was significantly increased when the drug was vehiculized in ASCn coagels, compared to other pharmaceutical systems. The results indicated that ASC12 seems to have the highest enhancing effect on FITC permeation. ASC12 appears to be the compd. that possesses the highest capacity to enhance the penetration of the drugs. Furthermore, it has the highest permeation of the serie.