title: Nanomedicine of anastrozole for breast cancer: Physicochemical evaluation, in vitro cytotoxicity on BT-549 and MCF-7 cell lines and preclinical study on rat model.
abstract: OBJECTIVE
  Formulation and evaluation of anastrozole, an anti-cancer drug loaded in different biodegradable polymeric nanoparticles.
  
  
  METHODS
  Different carrier systems such as poly(lactide-co-glycolide) (PLGA 50:50), poly(lactic-acid) (PLA) and poly(ε-caprolactone) (PCL) are used to prepare nanoparticles by simple emulsion technique. The surfactants polyvinyl alcohol and sodium deoxycholate were studied for their use as stabilizing agents at varying concentrations. The formulations were studied for their particle size, zeta potential, entrapment efficiency and solid state characteristics, and also were tested for their in vitro cytotoxicity and in vivo behavior in rats.
  
  
  RESULTS
  The entrapment ranged from 35 to 85%, depending on the drug-polymer ratio used. Particle size ranged from 100 to 350nm with optimal zeta potential. Accordingly, discrete spherical nanoparticles with smooth surface were obtained as evidence from Field Emission Scanning Electron Microscopy (FESEM) study. The solid state characteristics revealed dispersion of drug at the molecular level in the polymeric matrix of nanoparticles. A non-Fickian transport with initial burst release followed by slow release was observed with nanoparticles. The remarkable decrease in cell viability at various time points was observed for PLGA nanoparticles compared to other polymer matrices. The AUC(0→∞) of PLGA, PLA and PCL nanoparticles were found to be 4.77, 19.31 and 19.81 fold higher than (p<0.05) anastrozole in solution, respectively. Also, pharmacokinetics study revealed the long time circulation of anastrozole loaded polymeric nanoparticles.
  
  
  CONCLUSIONS
  The results suggest that developed nanoparticles could be used successfully for effective management of breast cancer chemotherapy.
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India; South Eastern Applied Material Research Centre (SEAM), WIT, Applied Technology Building, Waterford, Ireland. Electronic address: gopalshavi@gmail.com.
authors.forename: Gopal Venkatesh
authors.initials: GV
authors.lastname: Shavi
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Usha Yogendra
authors.initials: UY
authors.lastname: Nayak
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Naseer
authors.initials: N
authors.lastname: Maliyakkal
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India; Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), WIT, Cork Road, Waterford, Ireland.
authors.forename: Praful Balavant
authors.initials: PB
authors.lastname: Deshpande
authors.affiliation: South Eastern Applied Material Research Centre (SEAM), WIT, Applied Technology Building, Waterford, Ireland.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghavendra
authors.affiliation: Tranzderm Solutions, Brookings 57006, SD, USA.
authors.forename: Averineni Ranjith
authors.initials: AR
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Meka Sreenivasa
authors.initials: MS
authors.lastname: Reddya
authors.affiliation: Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Nayanabhirama
authors.initials: N
authors.lastname: Udupa
authors.affiliation: Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC), WIT, Cork Road, Waterford, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Shrawan
mesh_terms: D000077384:Anastrozole; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D050997:Nanomedicine; D053758:Nanoparticles; D009570:Nitriles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010316:Particle Size; D051381:Rats; D014230:Triazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole
keywords: Anastrozole; Cytotoxicity; PCL; PLA; PLGA; Pharmacokinetic study