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

• Published in: Pharmaceutical research Vol. 20; no. 2; pp. 237 - 246
• Main Authors: FARAASEN, Sofia, VÖRÖS, Janos, CSUCS, Gabor, TEXTOR, Marcus, MERKLE, Hans P, WALTER, Elke
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.02.2003; Springer Nature B.V
• Subjects: Adsorption; Biological and medical sciences; Cells, Cultured; Dendritic cells; Drug Delivery Systems - methods; General pharmacology; Humans; lactide-co-glycolide) (PLGA) microspheres; Ligands; Medical sciences; Microspheres; Molecular weight; NATURAL SCIENCES; NATURVETENSKAP; Peptides; Phagocytes - drug effects; Phagocytes - metabolism; phagocytosis; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasma; poly(D; poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG); Polyethylene Glycols - administration & dosage; Polyethylene Glycols - pharmacokinetics; Polylysine - administration & dosage; Polylysine - analogs & derivatives; Polylysine - pharmacokinetics; Polymers; Proteins; RGD-peptide; surface modification; Surface Properties; Surfactants; Switzerland; Glycolic acid copolymer; Human; Dendritic cell; Microsphere; Targeting; Ligand; Lactic acid copolymer; RGD-peptide; surface modification; Molecular interaction; Lysine polymer; poly(D,L,-lactide-co-glycolide) (PLGA) microspheres; In vitro; Blood; Ethylene oxide polymer; Microparticle; poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG); Coating; Conjugated compound; Phagocytosis; Macrophage; Phagocyte
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1023/A:1022366921298

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. 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. 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. 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.