Copolymeric Micelles for Delivery of EGCG and Cyclopamine to Pancreatic Cancer Cells.

Our objective was to synthesize a copolymer for delivery and protection of (-)-epigallocatechin gallate (EGCG). Methoxy poly(ethylene glycol)-b-poly[5-methyl-5-(3, 4, 5-trimethoxybenzoyol)-1, 3-dioxan-2-one-co-lactide] [mPEG-b-P(TM-co-LA)] copolymer was synthesized and characterized. The use of gallate containing monomer resulted in a copolymer that could show enhanced drug loading, stability, and sustained release of EGCG from mPEG-b-P(TM-co-LA) micelles as determined using LC/MS. The combination of EGCG and cyclopamine (CyA) displayed remarkable effects on growth inhibition of Mia PaCa-2 pancreatic cancer cells and induction of apoptosis. Although the expression level of Gli-1 was markedly downregulated by cyclopamine treatment, treatment with EGCG significantly inhibited the phosphorylation of EGFR in Mia PaCa-2 cells. Gallate containing copolymer can be used for micellar delivery of EGCG and CyA and the combination of these drugs can target 2 signaling pathways, thereby providing an effective way to treat pancreatic cancer. [ABSTRACT FROM AUTHOR]