Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue European Journal of Pharmaceutical Sciences Année : 2009

Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages.

Résumé

We evaluated the influence of ligand grafting on the rate and intensity of uptake of poly(d,l-lactide-co-glycolide) microparticles by alveolar macrophages. Microspheres with a mean diameter of 2.5 microm were obtained by spray drying. Three ligands (WGA, an RGD containing peptide and mannose-PEG(3)-NH(2)) and a cationic molecule (PLL) were covalently grafted on the particle surface using the carbodiimide method. Their grafting efficiency was quantified, and WGA grafting was characterized by confocal laser scanning microscopy (CLSM) and by atomic force microscopy (AFM). The uptake by macrophages of surface-modified microspheres was quantified by CLSM. This work showed that the uptake of negatively charged ligand-grafted microspheres (-26 to -51 mV) was increased up to two to four times according to the ligand compared to ungrafted microspheres (-81 mV) and displayed saturation as opposed to the cationic PLL-grafted microspheres. Moreover, a specific receptor-mediated phagocytosis mechanism was suggested based on free ligand, cytochalasin D and +4 degrees C incubation that decreased the microparticle uptake. Furthermore, this work clearly showed that the relative contribution of specific and non-specific processes to the overall uptake varied greatly according to the ligands, and was dependent on the particle-to-cell ratio. In conclusion, this work showed that ligand grafting can enhance the uptake of microparticles, with a variable relative contribution of specific and non-specific uptake mechanism.

Dates et versions

hal-00662974 , version 1 (25-01-2012)

Identifiants

Citer

Nolwenn Brandhonneur, François Chevanne, Véronique Vié, Benoît Frisch, Roselyne Primault, et al.. Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages.. European Journal of Pharmaceutical Sciences, 2009, 36 (4-5), pp.474-85. ⟨10.1016/j.ejps.2008.11.013⟩. ⟨hal-00662974⟩
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