Chengji Cui1, Steven P Schwendeman. 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109-1065, USA.
Abstract
PURPOSE: 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. MATERIALS AND 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.
PURPOSE: 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. MATERIALS AND 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.
Authors: Marian H Hettiaratchi; Tobias Miller; Johnna S Temenoff; Robert E Guldberg; Todd C McDevitt Journal: Biomaterials Date: 2014-05-28 Impact factor: 12.479