Ascorbic acid derivative-loaded modified aspasomes: formulation, in vitro, ex vivo and clinical evaluation for melasma treatment

Abstract

Vitamin C (L-Ascorbic acid) has many favourable effects on the skin such as antioxidant, anti-aging and whitening effects. Its instability and low permeability limit its pharmaceutical use in cosmetic and dermatological products. Instead, Mg ascorbyl phosphate (MAP), an ascorbic acid derivative, has the same effect with higher stability is being used. In this work, a vesicular system, aspasomes, containing MAP was developed and evaluated. Aspasomes are multilayered vesicles formed by amphiphiles molecules, Ascorbyl palmitate (ASP), in combination with cholesterol and charged lipids for drug encapsulation. Here, we investigated the use of lecithin instead of the charged lipid dicetyl phosphate for aspasomes development. Nine formulations were prepared and evaluated for their entrapment efficiency, particle size, polydispersity index (PDI) and zeta potential. Their entrapment efficiency ranged from 33.00 ± 2.27 to 95.18 ± 1.06, while their particle size was from 373.34 ± 60.85 to 464.37 ± 93.46 nm with acceptable PDI (from 0.212 ± 0.068 to 0.351 ± 0.061) and zeta potential (from −37.52 ± 2.42 to −50.36 ± 1.82). Three formulations were selected and evaluated for their drug release, permeation and retention into skin. One formulation was selected to be formulated as aspasomal topical cream and gel. The aspasomal cream was found to have enhanced drug permeation and skin retention over the aspasomal gel as well as the aspasomes formulation. MAP aspasomal cream was evaluated clinically as an effective treatment for melasma against 15% trichloroacetic acid (TCA) and the results recorded that the aspasomal cream showed the greatest degree of improvement regarding the hemi-MASI scores with 35% of patients rating it as excellent treatment. The study showed that MAP aspasomal cream can be considered a novel treatment of melasma which is free of side effects. Its efficacy as a monotherapy is superior to that of chemical peeling using 15% TCA.