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Artif Cells Nanomed Biotechnol ; 46(sup1): 773-786, 2018.
Article in English | MEDLINE | ID: mdl-29426248

ABSTRACT

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 1H 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.


Subject(s)
Cholesterol/chemistry , Curcumin/chemistry , Curcumin/pharmacology , Drug Carriers/chemistry , Micelles , Polyethylene Glycols/chemistry , Vitamin E/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Transport , Cell Line, Tumor , Drug Carriers/metabolism , Drug Liberation , Humans , Hydrophobic and Hydrophilic Interactions , Mice
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