title: In-vitro cytotoxicity and combination effects of the docetaxel-conjugated and doxorubicin-conjugated poly(lactic acid)-poly(ethylene glycol)-folate-based polymeric micelles in human ovarian cancer cells.
abstract: OBJECTIVE
  The pH-sensitive doxorubicin (DOX)-conjugated and docetaxel (DTX)-conjugated poly(lactic acid)-poly(ethylene glycol)-folate (PLA-PEG-FOL)-based polymeric micelles were developed and characterized in this study.
  
  
  RESULTS
  The drugs were released from the micelles (particle size, ~185 nm) in a pH-dependent manner. The drug-conjugated PLA-PEG-FOL micelles showed higher cellular uptake than nontargeting ones. Single agent and combination in-vitro cytotoxicity studies were also performed using the two drugs in both free and their micellar forms in SKOV3 human ovarian cancer cells using three different cytotoxicity assays. Like the free drugs, DOX-conjugated and DTX-conjugated targeting micelles showed significant cytotoxic effects in SKOV3 cell line. Moreover, the drug-conjugated targeting micelles improved cytotoxicity compared to the FOL-free ones. Different ratios of IC50of free drugs were used for combination therapy, and synergistic, additive or antagonistic effects were evaluated. The synergistic effect was observed in specific DOX : DTX mixing ratios, which result in the increase in therapeutic efficacy using low doses of each test compound without formulation related side effects.
  
  
  CONCLUSIONS
  The prepared micelles may provide appropriate delivery systems for doxorubicin and docetaxel in both single and combination therapies.
authors.affiliation: Department of Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.|Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hami
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.|Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Rezayat
authors.affiliation: Aerosol Research Laboratory, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Kambiz
authors.initials: K
authors.lastname: Gilani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghazi-Khansari
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D000077143:Docetaxel; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D065546:Drug Liberation; D004357:Drug Synergism; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; D043823:Taxoids; C552831:poly(ethylene glycol)-folate; D000077143:Docetaxel; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin; D005492:Folic Acid
keywords: cancer; micelle; nanoparticles; polymer synthesis; targeted drug delivery