Development of paclitaxel-TyroSpheres for topical skin treatment.
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 72 h 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 (IC(50) 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.
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Brian E
BE
Kilfoyle
Larisa
L
Sheihet
Zheng
Z
Zhang
Marissa
M
Laohoo
Joachim
J
Kohn
Bozena B
BB
Michniak-Kohn
D000279:Administration, Cutaneous; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014443:Tyrosine
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D014443:Tyrosine; D017239:Paclitaxel