In vitro and in vivo dermal absorption assessment of acetyl aspartic acid: a compartmental study.

OBJECTIVE: The purpose of this study was to evaluate the dermal absorption of acetyl aspartic acid (A-A-A) through an in vitro and in vivo evaluation with human skin after 6 and 24 h of topical application of a cosmetic formulation containing A-A-A at 1%. METHODS: The in vitro experiment was carried out using the Franz diffusion cells system with ex vivo human skin samples. The profile of diffusion of A-A-A was evaluated after 6 and 24 h. The in vivo experiment was performed on human volunteers following a tape-stripping protocol after 6 h of topical application. A-A-A was quantified in the main skin compartments, that is the skin surface, the stratum corneum, the skin and the receptor fluid using LC-MS analysis. RESULTS: The 24-h in vitro experiment confirmed the great penetration potential of A-A-A in all skin compartments. After 6 h of topical application, the removed tape strips from both in vitro and in vivo experiments were analysed and the profile of diffusion of A-A-A was determined, allowing also an in vitro/in vivo comparison. The diffusion profile observed on the in vitro skin penetration test is highly representative of the in vivo situation evaluated on volunteers. CONCLUSION: The combination of in vitro with in vivo data confirmed that A-A-A has the capacity to diffuse through the skin after topical application and reach the dermis as the targeted skin layer for potential anti-ageing benefits.

Pre-clinical formulation screening, development and stability of acetyl aspartic acid for cosmetic application.

BACKGROUND: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap). Using an in silico and in vitro approach, A-A-A was found increased keratinocyte regeneration, inhibited dermal expression of MMP making this compound a potential active ingredient for cosmetic application. OBJECTIVES: To determine the conditions to successfully formulate A-A-A for skin delivery investigation and in vivo clinical assessment by the systematic approach of pre-formulation testing of the active, screening of formulation type on active delivery and stability evaluations. METHODS: Analytical evaluation of A-A-A was undertaken using LC-MS ESI method. Formulation stability was evaluated using Brookfield viscometer, pH analysis, optical microscopy and organoleptic evaluations. RESULTS: Analytical evaluation of A-A-A shows that pH significantly impacts chemical stability of the molecule. A-A-A containing formulae show minimal differences to vehicle product throughout the testing. CONCLUSION: A-A-A is an active that can be successfully formulated in a cosmetic o/w emulsion within defined pH considerations.

Benzophenone-3 entrapped in solid lipid microspheres: formulation and in vitro skin evaluation.

Solid lipid microspheres (SLM), lipid-in-water formulations made from oil-and-wax mixtures, were studied concerning feasibility. SLMs were then loaded with a benzophenone-3, water insoluble UVAB-filter intended for dermal application. Microspheres were prepared by dispersion with homogenisers and investigated by polarizing micrography and scanning electron micrography. For the selected formulations, investigations on percutaneous penetration of B-3 capacity were performed "in vitro" using Franz cells. Microspheres, 5-50 µm in size, and a spherical shape were obtained from several mixtures. B-3 was added and the loading capacity of this drug in the SLM was obtained for a maximum of 5% when the lipophilic phase was 18%. The lipophilic mixture with non-ionic surfactants in the selected formulation of lipid microspheres has a favorable effect on size. The selected formulation is also cosmetically adapted and it is composed of physiological and biodegradable lipids. B-3 was released and penetrated into skin more quickly and in greater quantity than in SLM form, from vehicles containing free B-3. This work has shown that SLM is an excellent carrier for lipophilic sunscreens like B-3 in order to decrease the release and penetration rate of this UV absorber compared with B-3 in oily solution.