Cellular uptake of PEO surface-modified nanoparticles: evaluation of nanoparticles made of PLA:PEO diblock and triblock copolymers.
Nanoparticles with either physically adsorbed or covalently bound poly(ethylene oxide) (PEO) coatings were produced from various combinations of poly(lactic acid) (PLA) and diblock or triblock copolymers of PLA and PEO. The particles were produced by the salting-out process and purified by the cross-flow filtration technique. The amount of PEO at the nanoparticle surface, as well as the residual amount of emulsifier poly(vinyl alcohol) were assessed, with a good correlation with expected values. Stability of the nanoparticulate suspensions was studied at 4 degrees C and after freezing under various conditions for up to 6 months. The nanoparticle redispersibility after storage was related to the thermal behavior of the PEO coatings. The in vitro cellular uptake of the different types of nanoparticles was compared by flow cytometry after incubation with human monocytes in serum and in plasma. The influence of the PEO molecular weight and surface density on the particle uptake was especially marked for the diblock and triblock copolymer formulations, with a decrease in uptake of up to 65% with one of the diblock copolymer formulations. Nanoparticles made of triblock copolymer with short PEO chains at their surface in the postulated "loop conformation" proved to be as resistant to cellular uptake as nanoparticles made of diblock copolymers with PEO chains in the "brush conformation".
School of Pharmacy, University of Geneva, CH-1211 Geneva 4, Switzerland.
F
F
De Jaeghere
E
E
Allemann
J
J
Feijen
T
T
Kissel
E
E
Doelker
R
R
Gurny
D002460:Cell Line; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009000:Monocytes / Q000378:metabolism*; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011108:Polymers / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*
D011091:Polyesters; D011108:Polymers; D013501:Surface-Active Agents; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)