Development of paclitaxel-TyroSpheres for topical skin treatment

作者：Kilfoyle Brian E; Sheihet Larisa; Zhang Zheng; Laohoo Marissa; Kohn Joachim; Michniak Kohn Bozena B^*

来源：Journal of Controlled Release, 2012, 163(1): 18-24.

DOI：10.1016/j.jconrel.2012.06.021

• Psoriasis
• Topical drug delivery
• Tyrosine-derived nanospheres
• Cytotoxicity
• Skin distribution
• Viscous formulation

A potential topical psoriasis therapy has been developed consisting of tyrosine-derived nanospheres (TyroSpheres) with encapsulated anti-proliferative paclitaxel. TyroSpheres provide enhancement of paclitaxel solubility (almost 4000 times greater than PBS) by effective encapsulation and enable sustained, dose-controlled release over 72h under conditions mimicking skin permeation. TyroSpheres offer potential in the treatment of psoriasis, a disease resulting from over-proliferation of keratinocytes in the basal layer of the epidermis, by (a) enabling delivery of paclitaxel into the epidermis at concentrations > 100 ng/cm(2) of skin surface area and (b) enhancing the cytotoxicity of loaded paclitaxel to human keratinocytes (IC50 of paclitaxel-TyroSpheres was approximately 45% lower than that of free paclitaxel). TyroSpheres were incorporated into a gel-like viscous formulation to improve their flow characteristics with no impact on homogeneity, release or skin distribution of the payload. The findings reported here confirm that the TyroSpheres provide a platform for paclitaxel topical administration allowing skin drug localization and minimal systemic escape.

• 出版日期2012-10-10