In vivo targeting of inflamed areas by electroloaded neutrophils.
Due to their spontaneous accumulation in inflamed or infected areas, blood phagocytes are potent drug vectors with specific targeting. Drug like molecule loading was obtained by use of cell electropermeabilization in which the impermeability of their plasma membrane is transiently impaired. Electrical conditions were used which allow electroloading of a drug like molecule (propidium iodide) in 70% of leukocytes in a whole blood sample while preserving in vitro functional properties. Slow release of entrapped hydrophilic molecules was observed with a half lifetime longer than 4 hours at 4 degrees C and at 37 degrees C. With an in vivo assay, using a rat model of inflammation, we showed that, as for non-pulsed cells, pulsed neutrophils accumulate 10 times more in an inflamed area than they do in control areas. Phagocyte electropermeabilization is therefore a very efficient way of drug targeting. Accumulation of electropulsed neutrophils in an area of inflammation gives targeted release of the electroloaded drug.
Sixou
S
S
Centre de Recherche de Biochimie et de Génétique Cellulaires du CNRS, Toulouse, France.
Teissié
J
J
D000818:Animals; D002634:Chemotaxis, Leukocyte; D007249:Inflammation / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009504:Neutrophils / Q000000981:diagnostic imaging / Q000502:physiology*; D015609:Organotechnetium Compounds; D010091:Oximes; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D019690:Technetium Tc 99m Exametazime; D013997:Time Factors
D015609:Organotechnetium Compounds; D010091:Oximes; D019690:Technetium Tc 99m Exametazime