Ligand-specific targeting of microspheres to phagocytes by surface modification with poly(L-lysine)-grafted poly(ethylene glycol) conjugate.
OBJECTIVE
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.
Faraasen
Sofia
S
Laboratory of Applied Physics, Department of Physics and Measurement Technology, Linköping University, SE-581 83 Linköping, Sweden.
Vörös
János
J
Csúcs
Gábor
G
Textor
Marcus
M
Merkle
Hans P
HP
Walter
Elke
E
D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008863:Microspheres; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011107:Polylysine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013499:Surface Properties
D008024:Ligands; C443714:polylysine-graft-(poly(ethylene glycol)); D011107:Polylysine; D011092:Polyethylene Glycols