Ligand-specific targeting of microspheres to phagocytes by surface modification with poly(L-lysine)-grafted poly(ethylene glycol) conjugate

Purpose. The purpose of this study was to demonstrate specific receptor- mediated targeting of phagocytes by functional surface coatings of microparticles, shielding from nonspecific phagocytosis and allowing ligand- specific interactions via molecular recognition. Methods. Coatings of the comb polymer poly( L- lysine)- g-poly( ethylene glycol) (PLL- g- PEG) were investigated for potential to inhibit 1) nonspecific spreading of human blood- derived macrophages (MOs) and dendritic cells (DCs) on glass and 2) nonspecific phagocytosis of PLL- g- PEG- coated, carboxylated polystyrene (PS) or biodegradable poly( D, L- lactide- co- glycolide) (PLGA) microspheres. Coating was performed by adsorption of positively charged PLL- g- PEG on negatively charged microparticles or plasma- cleaned glass through electrostatic interaction. The feasibility of ligand-specific interactions was tested with a model ligand, RGD, conjugated to PEG chains of PLL- g- PEG to form PLL- g- PEG- RGD and compared with inactive ligand conjugate, PLL- g- PEG- RDG. Results. Coatings with PLL- g- PEG largely impaired the adherence and spreading of MOs and DCs on glass. The repellent character of PLL- g- PEG coatings drastically reduced phagocytosis of coated PS and PLGA microparticles to 10% in presence of serum. With both MOs and DCs, we observed ligand- specific interactions with PLL- g-PEG- RGD coatings on glass and PS and PLGA microspheres. Ligand specificity was abolished when using inactive ligand conjugate PLL- g- PEG- RDG, whereas repellency of coating was maintained. Conclusions. Coatings of PLL- g- PEG- ligand conjugates provide a novel technology for ligand specific targeting of microspheres to MOs and DCs while reducing nonspecific phagocytosis.