Nanocomposite gel containing usnic acid: Characterization and evaluation of the antibacterial efficacy on Staphylococcus epidermidis

Abstract

Usnic acid (UA) is one of the most abundant secondary metabolites of lichens. Its antibacterial, anti-inflammatory, antiviral, and antitumor properties make it one of the few commercially available lichens compounds. Owing to its low solubility it has limited application, for that reason encapsulation in polymeric micelles (UA-PM) has been used to solve this aspect. Then, the obtained dispersion has been incorporated into a Sepigel-based gel for skin application (UA-PM-GEL). Polymeric micelles consisting of Soluplus, Solutol HS15 and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) were characterized in terms of size, polydispersity index, Zeta potential and morphological analysis. The nanocomposite gel (UA-PM-GEL) was characterized by determining the rheological behaviour, pH, UA recovery, physical and chemical stability and texture characteristics during one-month storage. The dialysis bag method and vertical diffusion Franz cell apparatus were used to determine the UA release from UA-PM and UA-PM-GEL. Skin-PAMPA assay allowed to evaluate the influence of micelles and nanocomposite formulation on the in vitro passive permeability of UA. In addition, the antibacterial activity of UA-PM and UA-PM-GEL was evaluated on the Staphylococcus epidermidis bacterial strain. The micellar formulation significantly increased both the solubility and the permeability of the UA, as indicated by the Pe value obtained by Skin-PAMPA test. The release of the active ingredient, although more gradual than the colloidal dispersion, was not hindered by the viscosity of the gel system, as demonstrated by the release studies. The rheological properties of the gel outlined a good spreadability, adhesion and viscosity, suggesting easy application and removal from the application site. The pH values also proved to be suitable for skin application. The formulation was chemically and physically stable for 30 days, with a percentage of loss of the active ingredient less than 10 %. Finally, both the micelles and the nanocomposite gel revealed an effective antibacterial activity, representing a promising approach for the treatment of skin infections.

Keywords: Drug permeation; Nanocomposite gel; PAMPA; Polymeric micelles; Solubility; Staphylococcus epidermidis; Usnic acid.