Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment

•Synthesis of degradable multiblock polymeric nanomedicines.•Cytotoxicity of combination treatments determined by combination index analysis.•Sequential addition of nanomedicines to A2780 cells has an impact on cytotoxicity.•Two nanomedicines are more cytotoxic than a nanomedicine containing both dr...

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Veröffentlicht in:	International journal of pharmaceutics 2013-09, Vol.454 (1), p.435-443
Hauptverfasser:	Larson, Nate, Yang, Jiyuan, Ray, Abhijit, Cheney, Darwin L., Ghandehari, Hamidreza, Kopeček, Jindřich
Format:	Artikel
Sprache:	eng
Schlagworte:	animal ovaries Antineoplastic Combined Chemotherapy Protocols - pharmacology biodegradability Biodegradable polymers cathepsin B Cathepsin B - chemistry Cell Line, Tumor Cell Survival - drug effects Chemistry, Pharmaceutical Combination therapy composite polymers cytotoxicity Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives Deoxycytidine - chemistry Deoxycytidine - pharmacology Drug Carriers Drug Stability Drug Synergism drugs Female Gemcitabine HPMA copolymers Humans Hydrogen-Ion Concentration Hydrolysis in vitro studies Kinetics Male Molecular Weight Ovarian cancer ovarian neoplasms Ovarian Neoplasms - pathology Paclitaxel Paclitaxel - administration & dosage Paclitaxel - chemistry Paclitaxel - pharmacology Polymerization Polymethacrylic Acids - chemistry Solubility synergism Technology, Pharmaceutical - methods
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Zusammenfassung:	•Synthesis of degradable multiblock polymeric nanomedicines.•Cytotoxicity of combination treatments determined by combination index analysis.•Sequential addition of nanomedicines to A2780 cells has an impact on cytotoxicity.•Two nanomedicines are more cytotoxic than a nanomedicine containing both drugs. The synthesis, characterization, and in vitro evaluation of a combination delivery of multiblock poly(N-2-hydroxypropyl)methacrylamide (HPMA), gemcitabine (GEM) and paclitaxel (PTX) conjugates is described in this study. Multiblock copolymer conjugates of a large molecular weight (Mw>200kDa) were studied and compared to traditional, small molecular weight (Mw
ISSN:	0378-5173 1873-3476
DOI:	10.1016/j.ijpharm.2013.06.046