One-step surface modification of poly(lactide-co-glycolide) microparticles with heparin.
OBJECTIVE
The aim of this study was to modify the surface of poly(lactide-co-glycolide) (PLGA) microparticles with heparin. The heparin-coated PLGA may enhance blood and tissue compatibility of PLGA devices and provide a novel approach to deliver growth factors.


METHODS
A one-step method using heparin to replace traditional emulsifiers (e.g., PVA) during emulsion-solvent evaporation process was employed to surface-entrap heparin in PLGA microspheres. The emulsifying activity of heparin was modified via varying counter ion form, including univalent (Na(+), K(+), Li(+), and [Formula: see text]) and divalent (Ca(2+), Mg(2+), Ba(2+), and Zn(2+)) cations, and complexation with amino acids (Arg, Lys, Leu, Val, Gly and Glu). Surface accessible and total heparin loading were determined by a modified toluidine blue assay and elemental analysis, respectively.


RESULTS
Heparin bound with univalent counter ions and amino acids exhibited emulsifying activity to varying degrees, whereas divalent heparin salts tended to cause complete aggregation of the PLGA o/w emulsion. Increasing pH (>or=7.4) of hardening medium enhanced heparin adsorption and significantly stabilized the PLGA o/w emulsion. The initial surface density of heparin on the PLGA microspheres prepared using univalent heparin salts was around 8-33 mg/m(2). Surface associated heparin desorbed quickly; potassium heparin showed the best retention, with approximately 0.2 and 0.1 mg/m(2) detected on PLGA microsphere surface following 1- and 14-day incubation in PBST at 37 degrees C, respectively.


CONCLUSIONS
PLGA microparticles were successfully surface-modified with heparin. Univalent salts and amino acid complexes of heparin, as effective emulsifiers, can become surface-immobilized in PLGA microspheres.
Cui
Chengji
C
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109-1065, USA.
Schwendeman
Steven P
SP
D000596:Amino Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D045703:Emulsifying Agents / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D008863:Microspheres; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000596:Amino Acids; D004337:Drug Carriers; D045703:Emulsifying Agents; D008670:Metals; D009821:Oils; D011108:Polymers; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin
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