title: Highly efficient release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles enhances bone repair in rats.
abstract: Lovastatin exhibits higher thermal stability and lower degradation rate than simvastatin. However, the amount of research studying a lovastatin delivery device has been far less than similar research on simvastatin. As a consequence, a high lovastatin release rate system has not been developed. We hypothesized that highly efficient release of lovastatin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a short-term release (7 days) could provide an effective delivery system for bone repair. This study optimized the emulsion (o/w) technique in the fabrication process for PLGA nanoparticles, thereby producing the first recorded case of a high release rate (97%) of lovastatin. We also calculated the calibration curve of lovastatin using a UV spectrometer. The results demonstrated that the ALPase activity in human osteoblasts could be significantly stimulated by lovastatin carried in PLGA nanoparticles, but was prominently decreased by free lovastatin with the concentration higher than 4 µg/ml. Animal studies showed that the amount of lovastatin contained in 1 mg PLGA was the optimum dosage. These results suggest the new lovastatin-releasing PLGA delivery device exhibits potential for clinical treatment of bony defects.
authors.affiliation: Department of Chemical Engineering, Taiwan University of Science and Technology, Taipei 10600, Taiwan.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Ho
authors.forename: Chun-Pin
authors.initials: CP
authors.lastname: Chiang
authors.forename: Yao-Fang
authors.initials: YF
authors.lastname: Liu
authors.forename: Mark Yen-Ping
authors.initials: MY
authors.lastname: Kuo
authors.forename: Sze-Kwan
authors.initials: SK
authors.lastname: Lin
authors.forename: Juin-Yih
authors.initials: JY
authors.lastname: Lai
authors.forename: Bor-Shiunn
authors.initials: BS
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002478:Cells, Cultured; D054893:Cone-Beam Computed Tomography; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry; D008148:Lovastatin / Q000008:administration & dosage*; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects; D053758:Nanoparticles; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008148:Lovastatin; D000469:Alkaline Phosphatase