Microspheres made by w/o/o emulsion method with reduced initial burst for long-term delivery of endostar, a novel recombinant human endostatin

• Published in: Journal of pharmaceutical sciences 2009-06, Vol.98 (6), p.2051-2058
• Main Authors: Wu, Jinhui, Wu, Lin, Xu, Xiaoqiang, Xu, Xiangyang, Yin, Xiaojin, Chen, Yingjie, Hu, Yiqiao
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - blood; Angiogenesis Inhibitors - metabolism; Angiogenesis Inhibitors - pharmacology; Animals; Biodegradability; Biological and medical sciences; Cell Movement - drug effects; Cells, Cultured; Copolymers; Drug delivery; Drug Delivery Systems - methods; Drugs; Emulsions - chemistry; encapsulation; endostatin; Endostatins - administration & dosage; Endostatins - blood; Endostatins - metabolism; Endostatins - pharmacology; Endothelial Cells; General pharmacology; Humans; Medical sciences; microparticles; Microspheres; Molecular weight; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; pharmcokinetics; poly(lactic/glycolic) acid (PLGA or PLA); Polyglactin 910 - chemistry; polylactide-co-glycolide; protein delivery; Rats; Rats, Sprague-Dawley; Recombinant Proteins - administration & dosage; Recombinant Proteins - blood; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.21589

The purpose of this work is to design biodegradable Poly(lactide-co-glycolide) (PLGA) microspheres with low initial burst for sustained delivery of Endostar (a novel recombinant human endostatin) and investigate effects of PLGA molecular weight and composition on the release behavior of Endostar microspheres. Endostar microspheres were prepared by using novel w/o/o multiple emulsification–evaporation technique. Effects of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) have been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release and low initial burst were obtained with all microsphere formulations. The in vivo performance of Endostar microspheres were also found to be dependent on the polymer molecular weight and copolymer composition. Together, these results suggest that the initial burst release can be reduced by w/o/o emulsion method and the release of Endostar can be changed significantly by varying the polymer molecular weight and copolymer composition. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2051–2058, 2009