One-Step Surface Modification of Poly(lactide-co-glycolide) Microparticles with Heparin

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 ) and divalent (Ca²⁺, Mg²⁺, Ba²⁺, and Zn²⁺) 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 (≥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/m². Surface associated heparin desorbed quickly; potassium heparin showed the best retention, with ~0.2 and 0.1 mg/m² detected on PLGA microsphere surface following 1- and 14-day incubation in PBST at 37°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.