Drug Delivery to the Skin From Sub-micron Polymeric Particle Formulations: Influence of Particle Size and Polymer Hydrophobicity

Purpose  To investigate the influence of particle size and polymer properties on the topical delivery of a lipophilic “active” species (Nile Red (NR)) from sub-micron polymeric particles. Methods  Three poly-(ε-caprolactone) (CAPA) formulations were examined to assess the impact of particle size. Three other formulations, based on cellulose acetate butyrate (CAB), CAPA and polystyrene were studied to address the role of polymer hydrophobicity. In vitro skin permeation, and confocal microscopy and stratum corneum (SC) tape-stripping were used to evaluate the cutaneous disposition of NR. Results  NR delivery into the SC was greater from the larger particles, the overall smaller surface area of which enhanced the “leaving tendency” of the lipophilic “active”. Skin uptake of NR (measured as “%payload released”) from polystyrene, CAPA and CAB particles increased with decreasing polymer hydrophobicity (polystyrene > CAPA > CAB) as expected. Confocal microscopy revealed that NR released from the particles accumulated in, and penetrated via, lipid domains between the SC corneocytes. The particles showed affinity for hairs, and concentrated on the skin surface at the follicular openings. Conclusions  Delivery of a model drug to the skin from sub-micron polymeric particle formulations is sensitive to the particle size and the relative hydrophobicity of the carrier.