Polymeric micelles for cutaneous delivery of epigallocatechin gallate

The efficacy of epigallocatechin gallate (EGCG) in preventing skin ageing is known [1]. In particular, EGCG demonstrated to be effective in reducing the activity of proteinases in the skin collagenase. Moreover, it can protect the epidermis from damages induced by UVA, preventing the formation of UV-induced erythema. Considering the low skin penetration of UV rays, the design of delivery systems able to promote the EGCG localization into the epidermis resulted interesting to guarantee skin protection. However, the low solubility in water and low penetration through the skin and photostability have limited the use of EGCG in cosmetic products. The present study aimed to evaluate the feasibility of poloxamer micelles for improving the stability of EGCG and enhancing its penetration in the upper skin layers. EGCG-loaded polymeric micelles (0.1%, 0.2%, 0.3, 0.5% w/v) were prepared using solvent diffusion method (acetone solution/water: 1/10 v/v). Poloxamer 118 (P118) and 407 (P407) were selected as excipients because of their high solubility in water, other than the different molecular weight and HLB value. To study the impact of polymer composition on the physical properties and stability of EGCG-loaded polymeric micelles, different formulations were prepared using single polymer or 1:1 mixture at the final concentration of 1% w/v. The resulting nanosystems were characterized in terms of particle size, ζ-potential, apparent solubility of EGCG in water and the antioxidant activity of EGCG by DPPH assay. Their physical stability and the antioxidant activity was also checked over 1 month at room temperature. Poloxamers can auto-assemble in nano-micelles when EGCG was added to the formulation. The size of micelles ranged from 20 to 200 nm, as a function of their compositions; ζ-potential was around -10 mV for all formulations. Using micellar systems made of P407, the EGCG concentration can be increased up to 0.5% w/w without precipitate formation, whereas the maximum loading concentration is 0.2% w/v for P118 and 0.3% w/v for the mixtures of P407 and P118. The stability study suggested that micelles guarantee the chemical and antioxidant stability of EGCG. After 1 month from the preparation, a slight decrease of the EGCG amount was observed in the case of micelles made of P407 (<15%), whereas P118, alone or mixture, induced a decreased higher than 30%. In vitro permeation studies through full-thickness porcine ear skin will be performed by using Franz cells to evaluate the influence of micelles in enhancing the penetration pattern of EGCG.