title: Multipronged, strategic delivery of paclitaxel-topotecan using engineered liposomes to ovarian cancer.
abstract: BACKGROUND
  Synergistically active combinations have been used to enhance therapeutic efficacy for ovarian cancer chemotherapy.
  
  
  OBJECTIVE
  The synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) were loaded into folate-anchored PEGylated liposomes (FPL-Pac-Top) for safe and effective treatment of ovarian cancer.
  
  
  METHODS
  Coupling reactions were carried out using carbodiimide chemistry and confirmed by infrared spectral analysis. These liposomes were studied for shape and physical interaction (and integrity), in vitro drug release kinetics, hemolytic toxicity, ex vivo pharmacodynamics in OVCAR-3 cell lines, and pharmacokinetics in ovarian tumor-bearing mice.
  
  
  RESULTS
  The differential scanning calorimeter studies exhibited melting of liposomes (∼150 nm) at ∼41 °C. The drug(s) release from liposomes followed Fickian diffusion model. The hematological studies revealed insignificant toxicity to blood cells. In vivo studies showed long circulatory behavior (increased AUC0-tand AUMC0-tand MRT) and selective accumulation of FPL-Pac-Top in the ovaries. FPL-Pac-Top showed less necrosis and more apoptosis in flow cytometry. Kaplan-Meier survival analysis revealed the doubling of the survival time with FPL-Pac-Top in comparison to Pac-Top solution.
  
  
  CONCLUSIONS
  Potentiated anti-cancer activity of FPL-Pac-Top was attributed to multiple features viz. thermosensitivity, long circulatory nature and targetability. Such approach could be a paradigm chemotherapeutic approach for safe and effective targeting of cancer.
authors.affiliation: a Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University , Sagar , Madhya Pradesh , India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Jain
authors.affiliation: a Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University , Sagar , Madhya Pradesh , India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001773:Blood Cells / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D004338:Drug Combinations; D065546:Drug Liberation; D004357:Drug Synergism; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019772:Topotecan / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; D008081:Liposomes; D059004:Topoisomerase I Inhibitors; D011092:Polyethylene Glycols; D019772:Topotecan; D005492:Folic Acid; D017239:Paclitaxel
keywords: Ovarian cancer; ovcar-3; paclitaxel; thermo-sensitive liposomes; topotecan