Development and Characterization of a Topical Gel Formulation of Adapalene-TyroSpheres and Assessment of Its Clinical Efficacy

In this study we aimed to develop a semi-solid formulation of polymeric nanoparticles loaded with adapalene to enhance the efficacy and improve the skin tolerability in acne therapy. An amphiphilic and biocompatible copolymer that self-assembles to nanospheres (known as TyroSpheres) was used to encapsulate adapalene and increase its solubility. A water-soluble viscous agent was applied to prepare a gel formulation of adapalene-loaded TyroSpheres (aapalene-TyroSphere). Particle size, morphology, homogeneity, and rheological characteristics of the adapalene-TyroSphere gel formulations were studied. The formulation with the preferred physical and structural properties was further investigated for in vitro skin irritation and in vivo comedolytic activity in a rhino mouse model. Based on the in vitro skin irritation study encapsulation of adapalene in TyroSphere significantly decreased secretion of pro-inflammatory cytokines (IL-1α and IL-8), confirming that the TyroSphere formulation of adapalene is less irritant than the commercial gel (Differin). TyroSphere gel formulation of adapalene improved the comedolytic properties of the formulation by significantly reducing the size of open utricles in rhino mice compared to Differin treatment. Using TyroSpheres, we were able to develop an alternative topical formulation of adapalene, which is potentially less irritant and more potent than the commercial product.