Topical drug delivery by a polymeric nanosphere gel: Formulation optimization and in vitro and in vivo skin distribution studies

Tyrosine-derived nanospheres have demonstrated potential as effective carriers for the topical delivery of lipophilic molecules. In this investigation, a gel formulation containing nanospheres was developed for effective skin application and enhanced permeation. Carbopol and HPMC hydrophilic gels were evaluated for dispersion of these nanospheres. Sparingly water soluble diclofenac sodium (DS) and lipophilic Nile Red were used as model compounds. DS was used to determine the optimum polymer type, viscosity and release properties of the gel while fluorescent Nile Red was used in in vitro and in vivo skin distribution studies. In addition, the effect of a penetration enhancer, Azone, on the skin delivery was investigated. Dispersion of Nile Red-loaded nanospheres in 1% w/v HPMC gel produced a uniform and stable dispersion with suitable rheological properties for topical application, without any short-term cellular toxicity or tissue irritation. In vitro permeation studies using human cadaver skin revealed that the deposition of Nile Red via the nanosphere gel in the upper and lower dermis was 1.4 and 1.8 fold higher, respectively, than the amount of Nile Red deposited via an aqueous nanosphere formulation. In vivo, the HPMC gel containing Nile Red-loaded nanospheres significantly enhanced (1.4 fold) the permeation of Nile Red to the porcine stratum corneum/epidermis compared to the aqueous Nile Red-loaded nanospheres. An additional increase (1.4 fold) of Nile Red deposition in porcine stratum corneum/epidermis was achieved by incorporation of Azone (0.2 M) into the nanosphere gel formulation. Therefore, tyrosine-derived nanospheres dispersed in gels offer promise for the topical delivery of lipophilic drugs and personal care agents to skin for treatment of cancers, psoriasis, eczema, and microbial infections. (c) 2010 Elsevier B.V. All rights reserved.