title: Surface-modified Epirubicin-HCl liposomes and its in vitro assessment in breast cancer cell-line: MCF-7.
abstract: BACKGROUND
  Epirubicin-HCl is highly efficient for breast cancer management at a concentration of 60-90 mg/m(2). However, its application is limited due to cumulative dose-dependent cardio-toxicity.
  
  
  OBJECTIVE
  The main aim of this study was to formulate breast cancer-targeted liposomal carrier by surface conjugation of transferrin to minimize cardio-toxicity of drug along with improved pharmacokinetic profile.
  
  
  METHODS
  Liposomes were formulated by ethanol injection method using HSPC, cholesterol and DSPG and later loaded with drug by the ammonium sulfate gradient method. The formulation was characterized for physicochemical properties like size, zeta potential, entrapment efficiency, TEM; in vitro tests like electro-flocculation, hemolysis and drug release; cell line study (MCF-7 cells); in vivo studies including LD50 determination, pharmacokinetic analysis, myocardial toxicity determination and stability.
  
  
  CONCLUSIONS
  Optimized formulation had molar ratio of 60:30:8:2 (HSPC:Chol:DSPG:mPEG-DSPE) with entrapment efficiency ∼83%, particle size below 200 nm and zeta potential about -20 mV. In vitro studies proved non-interfering property and drug release character of formulation while cell line studies demonstrated improvement in cell uptake and thereby increased cytotoxicity of targeted formulation. The IC50 value obtained for epirubicin solution, non-targeted and targeted liposomes was 0.675, 0.532 and 0.192 µg/ml, respectively. Furthermore, in vivo tests validated safety and distribution profile of prepared formulations.
  
  
  CONCLUSIONS
  Apt properties of prepared Epirubicin-HCl liposomal formulation warrant its clinical application in breast cancer treatment after further studies.
authors.affiliation: a Pharmacy Department, Faculty of Technology and Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Gandhi
authors.affiliation: a Pharmacy Department, Faculty of Technology and Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
authors.forename: Nirav
authors.initials: N
authors.lastname: Khatri
authors.affiliation: a Pharmacy Department, Faculty of Technology and Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
authors.forename: Dipesh
authors.initials: D
authors.lastname: Baradia
authors.affiliation: a Pharmacy Department, Faculty of Technology and Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
authors.forename: Imran
authors.initials: I
authors.lastname: Vhora
authors.affiliation: a Pharmacy Department, Faculty of Technology and Engineering , The Maharaja Sayajirao University of Baroda , Vadodara , Gujarat , India.
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D015251:Epirubicin / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D008081:Liposomes; D061986:MCF-7 Cells; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D008055:Lipids; D008081:Liposomes; D014168:Transferrin; D011092:Polyethylene Glycols; D015251:Epirubicin; D002784:Cholesterol
keywords: Epirubicin; liposomes; pharmacokinetics; targeted drug delivery; transferrin