title: Sustained delivery of endostatin improves the efficacy of therapy in Lewis lung cancer model.
abstract: The purpose of this work was to develop an effective delivery system for antiangiogenic therapy. Endostatin was microencapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by using a w/o/o multiple emulsification-evaporation technique. Endostatin microspheres showed the encapsulation efficiency 100% with mean particle size about 25 microm. Endostatin released in vitro from PLGA microspheres were biologically active and significantly inhibited the migration of endothelial cells. In rats, endostatin microspheres produced a sustained release process in which the steady-state concentration was reached from day 5 to day 27 with the steady-state levels of endostatin between 174.8+/-33.3 and 351.3+/-126.3 ng/ml. In Lewis lung cancer model, a dose of 10 mg/kg endostatin microspheres was just as effective in suppressing tumor growth as a dose of 2 mg/kg/day free endostatin for 35 days (total dose 70 mg/kg). These results indicated PLGA microspheres further reduced the amount of endostatin needed to achieve significant tumor inhibition in mice when compared with systemic administration.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wu
authors.forename: Dawei
authors.initials: D
authors.lastname: Ding
authors.forename: Guoyan
authors.initials: G
authors.lastname: Ren
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xu
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Yin
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Hu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004195:Disease Models, Animal; D043169:Endostatins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D043169:Endostatins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid