Original ArticleDevelopment and characterization of polymeric nanoparticle-based formulation of adapalene for topical acne therapy
Graphical Abstract
An aqueous formulation based on tyrosine-derived nanospheres (TyroSpheres) was developed for topical delivery of adapalene, a comedolytic agent used in treatment of early stages of acne. Ex vivo skin distribution studies confirmed that TyroSpheres can enhance delivery of adapalene to upper skin layers and pilosebaceous unit, where acne originates. In vitro skin irritation studies showed that this new formulation of adapalene is less irritant compared to the commercial adapalene formulation.
Section snippets
Preparation and characterizations of adapalene-TyroSphere formulations
ABA triblock copolymer PEG5K-b-oligo(desaminotyrosyl-tyrosine octyl ester suberate)-b-PEG5K was used for the preparation of TyroSpheres. Adapalene-TyroSpheres and empty TyroSpheres (without drug) were prepared and purified by methods described previously.20, 21 The Nile Red-TyroSphere formulation was prepared as described previously,19, 20, 21, 22 using Nile Red TyroSphere ratio of 1:300 (w/w).
For characterization (see supplementary materials), the size and size distribution of
Adapalene-TyroSpheres: characterization of the liquid formulation
Due to its amphiphilic nature, PEG5K-b-oligo(DTO-SA)-b-PEG5K can self-assemble to form micellar-like spherical-shaped nanocarriers (TyroSpheres) in aqueous media and encapsulate hydrophobic drugs. Table 1 provides the solubility of adapalene in PBS either as loaded in the TyroSpheres or supplemented with various concentrations of Tween 80. Adapalene aqueous solubility in plain PBS pH 7.4 was below HPLC detection limit (10 ng/ml). The maximum solubility in 3% TyroSphere dispersion was
Discussion
Adapalene is a topical synthetic retinoid analog with anti-inflammatory properties that normalize differentiation of follicular epithelial cells.29 Adapalene is practically insoluble in aqueous media and possesses low solubility in many vehicles that make it very challenging to formulate. Topical application of retinoids can generate an adverse effect known as retinoid reaction, which is also reported at lower extend with adapalene commercial gel, Differin®.13 In Differin®, the drug exists in
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