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Abstract
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.
FUNDING
The authors would like to thank Dr. Ram I. Mahato for his support and careful review in the University of Tennessee Health Science Center as well as the National Natural Science Foundation of China (No. 21276198) and Science and Technology Commission of Shanghai Municipality (No. 12dz1909403) for financial support. Liming Sun is supported by Chinese Scholarship Council.