Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this
work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate
system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different
approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by
ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were
used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3).
In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic
liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta
potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency
and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2
and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size
of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased
up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method.
Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either
ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature,
rheological measurements and in vitro drug release studies. Results suggested that by increasing
P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both
cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly
lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo
controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and
volunteer’s satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results
indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region
and upper lip area and overall improvement in skin color and texture in most volunteers. There were
no instances of irritation, peeling or other apparent adverse side effects.
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