title: Micellar delivery of flutamide via milk protein nanovehicles enhances its anti-tumor efficacy in androgen-dependent prostate cancer rat model.
abstract: OBJECTIVE
  This article describes the preparation, physicochemical characterization and in vivo assessment of parenteral colloidal formulation of flutamide (FLT) based on biocompatible casein (CAS) self-assembled micelles in order to control drug release, enhance its antitumor efficacy and reduce its hepatotoxicity.
  
  
  METHODS
  Spray-drying technique was successfully utilized to obtain solidified redispersible drug-loaded micelles.
  
  
  RESULTS
  Spherical core-shell micelles were obtained with a particle size below 100 nm and a negative zeta potential above -30 mV exhibiting a sustained drug release up to 5 days. After intravenous administration into prostate cancer bearing rats for 28 days, FLT-loaded CAS micelles showed a higher antitumor efficacy as revealed by significantly higher reduction in PSA serum level (65.95%) compared to free FLT (55.43%). Moreover, micellar FLT demonstrated a marked decrease in relative weights of both prostate tumor and seminal vesicle (34.62 and 24.59%) compared to free FLT (11.86 and 17.74%), respectively. These antitumor responses were associated with notable reduction of cell proliferation, intratumoral angiogenesis and marked increase of tumor apoptosis. A significantly lower risk of hepatotoxicity was observed by micellar FLT as evidenced by lower alanine aminotransferase (ALT) serum level compared to free FLT.
  
  
  CONCLUSIONS
  Overall this approach suggested that CAS micelles might be an ideal candidate for intravenous delivery of hydrophobic anticancer drugs.
authors.affiliation: Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. dr_ahmedelzoghby@yahoo.com
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Elzoghby
authors.forename: Maged W
authors.initials: MW
authors.lastname: Helmy
authors.forename: Wael M
authors.initials: WM
authors.lastname: Samy
authors.forename: Nazik A
authors.initials: NA
authors.lastname: Elgindy
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000627:therapeutic use; D002364:Caseins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005485:Flutamide / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties
chemical_list: D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D002364:Caseins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D005485:Flutamide