Block Copolymer Based Composition of Epigallocatechin-3-gallate with Improved Oral Bioavailability as a Way to Increase its Therapeutic Activity

Abstract

At the present, a high potential of epigallocatechin-3-gallate (EGCG) as a new preventive and therapeutic agent in oncology and several other indications is well established. EGCG exerts its antitumor activity through induction of cell cycle arrest and apoptosis, inhibition of tumor angiogenesis, migration, and metastasisdue to its ability to interact with multiple targets in cancer cell. Unfortunately, very low oral bioavailability of EGCG prevents its efficient development as novel medicine. In this work, we have developed a polymer based nano-formulation of EGCG that significantly improved its oral bioavailability by increasing systemic exposure of the compound by about8-fold. This formulation comprises a well-known inactive ingredient non-ionic blockcopolymer Pluronic F127 that has recently been successfully used to increase bioavailability of another promising phytonutrient, 3,3`-diindolylmethane. The pharmacokinetic parameters established in the present study revealed that AUC and Cmax of the new formulation dosed at 500 mg/kg were 578.5 ± 73.8 μg∙h/mL and 49.3 ± 2.9 μg/mL, while in the case of control EGCG administered in the equivalent dose AUC and Cmax were 72.9 ± 14.7 μg∙h/mL, and 10.7 ± 1.1 μg/mL.