Pharmaceutical Research

, Volume 20, Issue 2, pp 237–246

Ligand-Specific Targeting of Microspheres to Phagocytes by Surface Modification with Poly(L-Lysine)-Grafted Poly(Ethylene Glycol) Conjugate

Authors

  • Sofia Faraasen
    • Laboratory of Applied Physics, Department of Physics and Measurement TechnologyLinköping University
    • Laboratory of Surface Science and Technology, Department of MaterialsSwiss Federal Institute of Technology Zurich (ETH)
    • Department of Applied Biosciences, Drug Formulation & Delivery GroupSwiss Federal Institute of Technology Zurich (ETH)
  • János Vörös
    • Laboratory of Surface Science and Technology, Department of MaterialsSwiss Federal Institute of Technology Zurich (ETH)
  • Gábor Csúcs
    • Biomicrometrics Group, Department of Mechanical EngineeringSwiss Federal Institute of Technology Zurich (ETH)
  • Marcus Textor
    • Laboratory of Surface Science and Technology, Department of MaterialsSwiss Federal Institute of Technology Zurich (ETH)
  • Hans P. Merkle
    • Department of Applied Biosciences, Drug Formulation & Delivery GroupSwiss Federal Institute of Technology Zurich (ETH)
    • Department of Applied Biosciences, Drug Formulation & Delivery GroupSwiss Federal Institute of Technology Zurich (ETH)
Article

DOI: 10.1023/A:1022366921298

Cite this article as:
Faraasen, S., Vörös, J., Csúcs, G. et al. Pharm Res (2003) 20: 237. doi:10.1023/A:1022366921298

Abstract

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.

poly(D,L,-lactide-co-glycolide) (PLGA) microspheressurface modificationpoly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG)phagocytosisRGD-peptide

Copyright information

© Plenum Publishing Corporation 2003