Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats.
The biological fate of injected foreign particles is believed to be closely related to their interactions with blood plasma proteins and cells. In order to verify this correlation, we have quantitatively measured protein adsorption and blood retention profiles in rats by using model polystyrene latex nanoparticles. The in vitro interactions of these non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic polymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. Protein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chromatography and field-flow fractionation. Pluronic F108 and Tetronic 908 and 1508 copolymers (with PEO terminal block MWPEO > 5000, PPO middle block MWPPO > 3000, and HLB values > 24) were shown to be the most effective surface modifiers in reducing adsorption of plasma proteins on the particles. Minimum interaction of coated particles with whole blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these block copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surface characteristics provided by such amphiphilic surface modifiers.
Tan
J S
JS
Life Sciences Research Laboratories, Eastman Kodak Company, Rochester, NY 14650.
Butterfield
D E
DE
Voycheck
C L
CL
Caldwell
K D
KD
Li
J T
JT
D000327:Adsorption; D000818:Animals; D001775:Blood Circulation; D001798:Blood Proteins / Q000737:chemistry*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000737:chemistry*; D006207:Half-Life; D007840:Latex; D008297:Male; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers; D011137:Polystyrenes / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents
D001798:Blood Proteins; D004337:Drug Carriers; D004852:Epoxy Compounds; D007840:Latex; D011108:Polymers; D011137:Polystyrenes; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C009068:propylene oxide