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

  • Sofia Faraasen
  • János Vörös
  • Gábor Csúcs
  • Marcus Textor
  • Hans P. Merkle
  • Elke Walter


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) microspheres surface modification poly(L-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) phagocytosis RGD-peptide 


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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Sofia Faraasen
    • 1
    • 2
    • 3
  • János Vörös
    • 2
  • Gábor Csúcs
    • 4
  • Marcus Textor
    • 2
  • Hans P. Merkle
    • 3
  • Elke Walter
    • 3
  1. 1.Laboratory of Applied Physics, Department of Physics and Measurement TechnologyLinköping UniversityLinköpingSweden
  2. 2.Laboratory of Surface Science and Technology, Department of MaterialsSwiss Federal Institute of Technology Zurich (ETH)SchlierenSwitzerland
  3. 3.Department of Applied Biosciences, Drug Formulation & Delivery GroupSwiss Federal Institute of Technology Zurich (ETH)ZurichSwitzerland
  4. 4.Biomicrometrics Group, Department of Mechanical EngineeringSwiss Federal Institute of Technology Zurich (ETH)SchlierenSwitzerland

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