| Abstract
| - A series of poly(lactic acid)−poly(ethylene oxide) (PLA−PEG) AB block copolymers have been synthesizedand used to produce aqueous dispersions of micellar-like nanoparticles. The hydrodynamic radius of thePLA core plus the stabilizing 5 kDa PEG layer, as determined by photon correlation spectroscopy, increasedwith the molecular weight of the PLA block. PLA−PEG particles have possible application as drug carriersfor targeted drug delivery. In addition to particle size, the layer thickness and mobility of the hydratedPEG chains will be important in determining the particle's ability to avoid uptake by the defense systemof the body, the phagocytic cells of the reticuloendothelial system. Viscoelastic measurements were usedto investigate interparticle interactions in concentrated dispersions of the PLA−PEG nanoparticles. Thisapproach has not previously been used to study how the interactions in dispersions of micellar-like assembliesdepend on the copolymer geometry. When the volume fraction of the dispersions, φcore, was increased, thestorage modulus, G‘, became greater than the loss modulus, G‘ ‘, indicating steric interaction between thePEG chains. At higher φcore values, compression of the grafted polymer chains was observed. The criticalvolume fraction at which overlap of the PEG chains commences, φcorecrit (i.e., G‘ = G‘ ‘), was used in conjunctionwith the overall hydrodynamic radius to determine the grafted PEG chain layer thickness. Micellar-likenanoparticles assembled from a PLA−PEG copolymer with a 5 kDa PEG block and a relatively low molecularweight 3 kDa PLA chain had an appreciable steric layer thickness of 6.3 nm. Hence, interparticle interactionsin the concentrated dispersion were “soft” in nature as a result of the long-range interactions, as shownby the weak scaling dependence of the storage modulus on the volume fraction. The layer became moreextended as the molecular weight of the PLA block was increased from 3 to 6 kDa, and as a consequencethe PEG chains became less compressible. By using this method to characterize the PEG layer, it shouldbe possible to rationalize the in vivo performance of the PLA−PEG nanoparticles and therefore aid thedesign of particulate drug carriers.
|
