Chitosan nanoparticles enhance the plasma exposure of (−)-epigallocatechin gallate in mice through an enhancement in intestinal stability

Abstract

The green tea catechin (−)-epigallocatechin gallate (EGCG) has attracted significant research interest due to its beneficial therapeutic effects, which include anti-oxidant, neuro-protective and anti-cancer effects. However, the therapeutic potential of EGCG following oral consumption is limited by its poor absorption. To address this issue, EGCG has been encapsulated in chitosan-tripolyphosphate nanoparticles (CS NPs) and the oral absorption of EGCG evaluated in Swiss Outbred mice. Administration of the CS NPs enhanced the plasma exposure of total EGCG by a factor of 1.5 relative to an EGCG solution, with plasma AUC (0 − 5 h) values of 116.4 ± 4.1 and 179.3 ± 10.8 nM.h (mean ± s.d., n = 3 − 5) for the EGCG solution and CS NPs, respectively. Associated with the increased plasma exposure of EGCG was an enhancement in concentrations of EGCG in the stomach and jejunum of mice following CS NP administration. A 2.3-fold increase in the apparent exposure of EGCG to the jejunum (AUC j) was observed following CS NP encapsulation, with AUC j(0 − 5 h) values of 5.3 ± 1.1 and 12.3 ± 1.5 μM.h (mean ± s.d., n = 3 − 5) for the EGCG solution and CS NPs, respectively. The enhanced exposure of EGCG to the jejunum was likely responsible for the increased plasma concentrations of EGCG. The findings from this study suggest that CS NPs may be a useful approach for enhancing oral delivery, and therapeutic application, of EGCG in a number of disease conditions.