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Cholesterol and vitamin E-conjugated PEGylated polymeric micelles for efficient delivery and enhanced anticancer activity of curcumin: evaluation in 2D monolayers and 3D spheroids.
Artificial Cells, Nanomedicine, and Biotechnology 2018 Februrary 10
A newly synthesized PEGylated cholesterol/α-tocopheryl succinate (α-TOS) linked polymer (CV) was self-assembled and loaded with curcumin to form a micellar system (C-CVM). The tri-functionalized amphiphilic polymer was constituted of hydrophobic cholesterol and α-TOS connected to hydrophilic PEG via a lysine linker. The synthesized polymer and the micelles were characterized by 1 H NMR, DLS, zeta potentiometer, TEM, CMC determination and hemolysis studies. CVM displayed low CMC value of 15 µM with extent of hemolysis as less than 4%. The stable C-CVM with optimum % drug loading (14.2 ± 0.24) displayed Z average of 175.8 ± 0.68 nm with PDI (0.248 ± 0.075) and released curcumin in sustained manner in the in vitro drug release study. C-CVM demonstrated dose-dependent cellular uptake and cytotoxicity in murine melanoma, B16F10 and human breast cancer, MDA-MB-231 cell lines. CV exhibited marked reversal of drug resistance as indicated by significantly higher retention of P-glycoprotein substrate, rhodamine-123 in the resistant B16F10 cell line compared to standard P-glycoprotein inhibitor, verapamil. C-CVM demonstrated significantly higher spheroidal growth inhibition compared to C-PPM. The results provide strong evidence for CVM as promising drug delivery system and confirm the potential of C-CVM as chemotherapy in cancer.
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