title: Raloxifene nanomicelles reduce the growth of castrate-resistant prostate cancer.
abstract: BACKGROUND
  Castrate-resistant prostate cancer (CRPC) patients are characterised by a 5-year relative survival rate of ∼25-33%. Recently, our laboratory encapsulated a selective oestrogen receptor modulator, raloxifene, into poly(styrene-co-maleic acid) (SMA-raloxifene), which demonstrated superior in vitro cytotoxicity compared with free drug against several CRPC cell lines.
  
  
  OBJECTIVE
  To validate SMA-raloxifene for the management of CRPC using a mouse xenograft model.
  
  
  METHODS
  The internalisation and retention of micellar and free raloxifene in vitro were measured by HPLC. A PC3-CRPC xenograft model was used to compare the biodistribution of both raloxifene formulations, as well as their effect on tumour progression where mice received free raloxifene (1 or 5 mg/kg, i.v.) or SMA-raloxifene (1 mg/kg, i.v.) weekly for 4 weeks.
  
  
  RESULTS
  SMA-raloxifene exhibited 75% higher intracellular content compared to free drug after 48 h in PC3 cells. Biodistribution of raloxifene was 69% higher in tumours following SMA-raloxifene compared with free raloxifene. Weekly administration of 1 mg/kg free raloxifene reduced tumour progression by 20% after 4 weeks, whereas 1 mg/kg SMA-raloxifene and 5 mg/kg free raloxifene reduced progression by 40%.
  
  
  CONCLUSIONS
  Encapsulation of raloxifene increased its therapeutic potential for the management of CRPC.
authors.affiliation: a Department of Pharmacology and Toxicology , University of Otago , Dunedin , New Zealand.
authors.forename: Tara
authors.initials: T
authors.lastname: Pritchard
authors.affiliation: a Department of Pharmacology and Toxicology , University of Otago , Dunedin , New Zealand.
authors.forename: Rhonda J
authors.initials: RJ
authors.lastname: Rosengren
authors.affiliation: a Department of Pharmacology and Toxicology , University of Otago , Dunedin , New Zealand.
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.affiliation: a Department of Pharmacology and Toxicology , University of Otago , Dunedin , New Zealand.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Taurin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018450:Disease Progression; D006801:Humans; D008297:Male; D008298:Maleates / Q000737:chemistry; D051379:Mice; D008823:Micelles; D011137:Polystyrenes / Q000737:chemistry; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; D020849:Raloxifene Hydrochloride
keywords: Biodistribution; castrate resistant prostate cancer; enhanced permeability and retention effect; nanomedicine; raloxifene