Sustained release of low molecular weight heparin from PLGA microspheres prepared by a solid-in-oil-in-water emulsion method.
Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres for the sustained release of low molecular weight heparin (LMWH) were prepared by a soild-in-oil-in-water (s/o/w) emulsion method. Prior to encapsulation, the LMWH micro-particles were fabricated by a modified freezing-induced phase separation method. The micro-particles were subsequently encapsulated into PLGA microspheres. Process optimization revealed that the NaCl concentration in the outer phase of s/o/w emulsion played a critical role in determining the properties of the microspheres. When the NaCl concentration increased from 0% to 5%, the encapsulation efficiency significantly increased from 51.5% to 76.8%. The initial burst release also decreased from 37.3% to 12.4%. In vitro release tests showed that LMWH released from PLGA microspheres in a sustained manner for about 14 days. Single injection of LMWH-loaded PLGA microspheres into rabbits resulted in an elevation of an anti-factor Xa activity for about 6 days. Furthermore, the integrity of the encapsulated LMWH was preserved during encapsulation process.
College of Life Science, Hebei Normal University, 113 Yuhua East Road, Shijiazhuang City, Hebei Province 050016, People's Republic of China. he_jintian@yahoo.com
Jintian
J
He
Zhitao
Z
Zhou
Yangyang
Y
Fan
Xianglian
X
Zhou
Huijuan
H
Du
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004339:Drug Compounding; D004655:Emulsions / Q000737:chemistry*; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits
D000925:Anticoagulants; D003692:Delayed-Action Preparations; D004655:Emulsions; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015951:Factor Xa