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. PURPOSE: 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%. CONCLUSION: Encapsulation of raloxifene increased its therapeutic potential for the management of CRPC.
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. PURPOSE: 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%. CONCLUSION: Encapsulation of raloxifene increased its therapeutic potential for the management of CRPC.
Authors: Usama A Fahmy; Shaimaa M Badr-Eldin; Hibah M Aldawsari; Nabil A Alhakamy; Osama A A Ahmed; Mohamed F Radwan; Basma G Eid; Shaban R M Sayed; Gamal A El Sherbiny; Walaa Abualsunun Journal: Drug Deliv Date: 2022-12 Impact factor: 6.819
Authors: Neha N Parayath; Hayley Nehoff; Samuel E Norton; Andrew J Highton; Sebastien Taurin; Roslyn A Kemp; Khaled Greish Journal: Int J Nanomedicine Date: 2016-08-17