The angiogenic effect of ONO-1301, a novel long-acting prostacyclin agonist loaded in PLGA microspheres prepared using different molecular weights of PLGA, in a murine sponge model.
The purpose of this study was to evaluate the angiogenic effect of topical application of three types of ONO-1301-loaded poly (lactide-co-glycolide) microspheres (ONO-1301 PLGA MS). ONO-1301 PLGA MS were prepared with PLGA 5010, 5020 and 5050 (with molecular weights of 10 K, 20 K and 50 K, respectively), using the solvent evaporation method. The lactide:glycolide ratio was fixed at 50:50; only the molecular weight was varied. The microspheres had an average diameter of almost 25 µm, and a loading efficiency of at least 70%. The sustained-release effect and its dependence on the molecular weight of the polymer used was confirmed in an in vitro drug-release test and by measuring subcutaneous plasma levels after administration of the three types of ONO-1301 PLGA MS to rats for 28 days. In the murine sponge model, the three types of ONO-1301 PLGA MS were administered to mice in a subcutaneously placed sponge and hemoglobin and hepatocyte growth factor (HGF) levels in the sponge were measured at predefined intervals up to 28 days. The hemoglobin and HGF levels obtained were significantly higher than those obtained after daily administration of ONO-1301 powder. Additional in vivo fluorescence imaging showed that PLGA MS remained in the sponge for 28 days. In conclusion, the three types of ONO-1301 PLGA MS prepared with PLGA three different molecular weight suppress the burst release, stimulate angiogenesis on topical application in a murine sponge model. This formulation may therefore be capable of improving the clinical picture in some types of vascular disease.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University , Hyogo , Japan and.
Mai
M
Hazekawa
Kana
K
Morihata
Miyako
M
Yoshida
Yoshiki
Y
Sakai
Takahiro
T
Uchida
D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D065546:Drug Liberation; D011464:Epoprostenol / Q000819:agonists*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats
D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D011725:Pyridines; C105488:ONO 1301; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011464:Epoprostenol
Angiogenesis; HGF; hemoglobin; in vivo fluorescence imaging; sustained-release