title: Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats.
abstract: OBJECTIVE
  To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.
  
  
  METHODS
  The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres.
  
  
  RESULTS
  rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10,000 or 30,000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R(2)=0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10,000 or 30,000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO.
  
  
  CONCLUSIONS
  The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.
authors.affiliation: College of Life Science, Hebei Normal University, Shijiazhuang, China.
authors.forename: Xiang-lian
authors.initials: XL
authors.lastname: Zhou
authors.forename: Jin-tian
authors.initials: JT
authors.lastname: He
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Du
authors.forename: Yang-yang
authors.initials: YY
authors.lastname: Fan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong-xia
authors.initials: HX
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D004655:Emulsions; D004921:Erythropoietin / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D004655:Emulsions; D011994:Recombinant Proteins; D004921:Erythropoietin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid