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  • Title: Improved bioavailability of orally administered mifepristone from PLGA nanoparticles.
    Author: He W, Horn SW, Hussain MD.
    Journal: Int J Pharm; 2007 Apr 04; 334(1-2):173-8. PubMed ID: 17101249.
    Abstract:
    The objective of this study was to prepare an oral dosage formulation of mifepristone that will improve the oral bioavailability of mifepristone and sustain the release of mifepristone for at least 3 days to effectively control reproduction, especially in coyotes. Nanoparticles containing mifepristone were prepared from dl-lactide/glycolide copolymers (PLGA). Encapsulation efficiency of the nanoparticles was determined by HPLC. In vitro release study was done in 30% isopropyl alcohol in water. In vivo bioavailability study was performed in male rats. Mifepristone and drug-loaded 50/50 PLGA, M(W) 4.4kDa, nanoparticles (equivalent to 100mg/kg mifepristone) were administered orally to rats. The concentration of mifepristone in serum at different time intervals was determined by HPLC. The average sizes of 50/50 PLGA (M(W) 4.4 and 13kDa) nanoparticles containing mifepristone were 516 and 468nm, respectively. The drug encapsulation efficiency was 75.6% at 20% drug loading in 50/50 PLGA (M(W) 4.4kDa) nanoparticles. In vitro cumulative release of mifepristone from the 50/50 PLGA (M(W) 4.4 and 13kDa) nanoparticles with 20% drug loading was 60% and 48% in 72h, respectively. In vivo studies in rats demonstrated that PLGA-1A-nanoparticles increase the bioavailability of mifepristone. We are currently using the nanoparticles containing mifepristone for efficacy studies in coyotes.
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