Design, synthesis and evaluation of N-acetyl glucosamine (NAG)-PEG-doxorubicin targeted conjugates for anticancer delivery.
Efficacy of anticancer drug is limited by the severe adverse effects induced by drug; therefore the crux is in designing delivery systems targeted only to cancer cells. Toward this objectives, we propose, synthesis of poly(ethylene glycol) (PEG)-doxorubicin (DOX) prodrug conjugates consisting N-acetyl glucosamine (NAG) as a targeting moiety. Multicomponent system proposed here is characterized by (1)H NMR, UV spectroscopy, and HPLC. The multicomponent system is evaluated for in vitro cellular kinetics and anticancer activity using MCF-7 and MDA-MB-231 cells. Molecular modeling study demonstrated sterically stabilized conformations of polymeric conjugates. Interestingly, PEG-DOX conjugate with NAG ligand showed significantly higher cytotoxicity compared to drug conjugate with DOX. In addition, the polymer drug conjugate with NAG and DOX showed enhanced internalization and retention effect in cancer cells, compared to free DOX. Thus, with enhanced internalization and targeting ability of PEG conjugate of NAG-DOX has implication in targeted anticancer therapy.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, India.
Smita K
SK
Pawar
Archana J
AJ
Badhwar
Firuza
F
Kharas
Jayant J
JJ
Khandare
Pradeep R
PR
Vavia
D000117:Acetylglucosamine / Q000008:administration & dosage / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008301:Maleimides / Q000737:chemistry; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008301:Maleimides; D011355:Prodrugs; C043592:maleimide; D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol; D000117:Acetylglucosamine