Pharmacokinetics of the green tea derivative, EGCG, by the topical route of administration in mouse and human skin

Abstract

Purpose: (−)-Epigallocatechin gallate (EGCG), the main physiologically active polyphenol of green tea, is associated with antitumor and antimutagenic activities. The goal of this study was to determine the stability and pharmacokinetic parameters of pure EGCG administered topically to human and mouse skin. Methods: EGCG was investigated by measuring drug levels of a 10% ointment formulation stored under different conditions over a period of 6 months. To determine pharmacokinetic parameters of EGCG following topical application, EGCG was applied as 10% EGCG in hydrophilic ointment USP to full-thickness mouse or human skin in vitro. The transdermal and intradermal. Penetration of EGCG was measured by reverse phase HPLC assays at different time-points. Results: The stability of EGCG in hydrophilic ointment USP was dependent on time, temperature and the degree of oxidation. For example, 10% EGCG was lost after 2 days at 37 °C, but the same formulation supplemented with 0.1% butylated hydroxytoluene (BHT) had significantly longer stability with ≥90% EGCG remaining after 130 days at 37 °C. Topical application of EGCG in hydrophilic ointment USP to human or mouse skin resulted in substantial intradermal uptake of up to 1–20% of the applied dose. However, transdermal penetration was observed only in mouse skin. Conclusion: The present study showed that topical application of EGCG in hydrophilic ointment USP achieved high concentrations in skin but negligible systemic availability. The drug was susceptible to oxidation, but if supplemented with BHT, the hydrophilic ointment formulation could potentially be used in clinical trials of skin cancer prevention.