Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system.
Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l-lactic acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA and PLA by the precipitation-solvent diffusion method. These nanoparticles, labeled by introducing [14C]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.
Bazile
D
D
Pharmaceutical Sciences Department, Institut de Biopharmacie, Antony, France.
Prud'homme
C
C
Bassoullet
M T
MT
Marlard
M
M
Spenlehauer
G
G
Veillard
M
M
D000818:Animals; D001345:Autoradiography; D003124:Colorimetry; D004337:Drug Carriers; D066298:In Vitro Techniques; D007773:Lactates / Q000138:chemical synthesis* / Q000302:isolation & purification; D019344:Lactic Acid; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010587:Phagocytosis; D011091:Polyesters; D011092:Polyethylene Glycols / Q000032:analysis / Q000138:chemical synthesis* / Q000302:isolation & purification; D011108:Polymers / Q000138:chemical synthesis* / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014018:Tissue Distribution
D004337:Drug Carriers; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol