Elasticity of vesicles affects hairless mouse skin structure and permeability

One of the possibilities for increasing the penetration rate of drugs throu gh the skin is the use of vesicular systems. Currently, special attention i s paid to the elastic properties of liquid-state vesicles, which are suppos ed to have superior properties compared to gel-state vesicles with respect to skin interactions. in this study, the effects of vesicles on hairless mo use skin, both in vivo and in vitro, were studied in relation to the compos ition of vesicles. The interactions of elastic vesicles containing the sing le chain surfactant octaoxyethylene laurate-ester (PEG-8-L) and sucrose lau rate-ester (L-595) with hairless mouse skin were studied. in vivo, after no n-occlusive application for 1, 3 and 6 h. The skin ultrastructure was exami ned by ruthenium tetroxide electron microscopy (TEM) and histology. The ext ent, to which vesicle constituents penetrated into the stratum corneum, was quantified by thin layer chromatography (TLC). The interactions of the ela stic vesicles containing PEG-g-L and L-595 surfactants were compared with t hose observed after treatment with rigid vesicles containing the surfactant sucrose stearate-ester (Wasag-7). Furthermore, skin permeability experimen ts were carried out to investigate the effect of treatment with PEG-8-L mic elles, elastic vesicles (containing PEG-8-L and L-595 surfactants) or rigid Wasag-7 vesicles on the (H2O)-H-3 transport through hairless mouse skin, i n vitro, after non-occlusive application. Treatment of hairless mouse skin with the elastic vesicles affected the ultrastructure of the stratum corneu m: distinct regions with lamellar stacks derived from the vesicles were obs erved in intercellular spaces of the stratum corneum. These stacks disrupte d the organization of skin bilayers leading to an increased skin permeabili ty, whereas no changes in the ultrastructure of the underlying viable epide rmis were observed. Treatment with rigid Wasag-7 vesicles did not affect th e skin ultrastructure or skin permeability. TLC measurements showed that af ter 1 h of non-occlusive application of elastic or rigid vesicles, a six-fo ld increased amount of elastic vesicle material was present within the stra tum corneum compared to rigid vesicle material. After 3 and 6 h of applicat ion the amount of PEG-8-L vesicle material in SC decreased to approximately three- and two-fold, respectively, compared to Wasag-7 vesicle material. P retreatment of the hairless mouse skin with the elastic vesicles containing 70 mol% PEG-8-L increased the diffusion of (H2O)-H-3 with an optimum appli cation dose of 2.5 mg lipids/cm(2) compared to PBS pretreatment. No signifi cant difference in the enhancement of the (H2O)-H-3-diffusion was observed between PEG-8-L micelles or elastic vesicles containing 30 or 70 mol% PEG-8 -L. Pretreatment with the rigid Wasag-7 vesicles decreased the diffusion ra te of (H2O)-H-3, most probably by the formation of a lipid layer on the ski n surface. The effect of the elastic vesicles on the skin permeability is s upported by the ultrastructural changes observed by TEM in the intercellula r lipid domains. The elastic vesicles containing 70 mol% PEG-8-L disorganiz e the lipid bilayers thereby creating or modifying pathways for possible dr ug penetration. (C) 1999 Elsevier Science B.V. All rights reserved.