title: Development of lovastatin-loaded poly(lactic acid) microspheres for sustained oral delivery: in vitro and ex vivo evaluation.
abstract: BACKGROUND
  A novel lovastatin (LVT)-loaded poly(lactic acid) microsphere suitable for oral administration was developed in this study, and in vitro and in vivo characteristics were evaluated.
  
  
  METHODS
  The designed microspheres were obtained by an improved emulsion-solvent evaporation method. The morphological examination, particle size, encapsulation ratio, drug loading, and in vitro release were characterized. Pharmacokinetics studies were used to show that microspheres possess more advantages than the conventional formulations.
  
  
  RESULTS
  By using the emulsion-solvent evaporation method, it was simple to prepare microspheres and easy to scale up production. The morphology of formed microspheres showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the microspheres was 2.65±0.69 μm; the encapsulation efficiency was 92.5%±3.6%, and drug loading was 16.7%±2.1%. In vitro release indicated that the LVT microspheres had a well-sustained release efficacy, and ex vivo studies showed that after LVT was loaded to microspheres, the area under the plasma concentration-time curve from zero to the last measurable plasma concentration point and the extrapolation to time infinity increased significantly, which represented 2.63-fold and 2.49-fold increases, respectively, compared to suspensions. The rate of ex vivo clearance was significantly reduced.
  
  
  CONCLUSIONS
  This research proved that poly(lactic acid) microspheres can significantly prolong the drug circulation time in vivo and can also significantly increase the relative bioavailability of the drug.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Qigang
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Department of Pharmaceutical, Shenyang Institute of Pharmaceutical Industry, Shenyang, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical, Shenyang Institute of Pharmaceutical Industry, Shenyang, People's Republic of China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D004355:Drug Stability; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008148:Lovastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008863:Microspheres; D008968:Molecular Conformation; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D013499:Surface Properties
chemical_list: D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D008148:Lovastatin
keywords: PLA; in vitro release; lovastatin; microspheres; pharmacokinetics