Specific and non-specific phagocytosis of ligand-grafted PLGA microspheres by macrophages.
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.
Brandhonneur
Nolwenn
N
Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, UPRES EA 3892, 2 avenue du professeur Léon Bernard, 35043 Rennes Cedex, France.
Chevanne
François
F
Vié
Véronique
V
Frisch
Benoît
B
Primault
Roselyne
R
Le Potier
Marie-Frédérique
MF
Le Corre
Pascal
P
D019344:Lactic Acid / Q000378:metabolism*; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D008024:Ligands; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid