Use of Viscoelastic Measurements for Investigating Interparticle Interactions in Dispersions of Micellar-like Poly(lactic acid)−Poly(ethylene glycol) Nanoparticles

Abstract

A series of poly(lactic acid)-poly(ethylene oxide) (PLA-PEG) AB block copolymers have been synthesized and used to produce aqueous dispersions of micellar-like nanoparticles. The hydrodynamic radius of the PLA core plus the stabilizing 5 kDa PEG layer, as determined by photon correlation spectroscopy, increased with the molecular weight of the PLA block. PLA-PEG particles have possible application as drug carriers for targeted drug delivery. In addition to particle size, the layer thickness and mobility of the hydrated PEG chains will be important in determining the particle's ability to avoid uptake by the defense system of the body, the phagocytic cells of the reticuloendothelial system. Viscoelastic measurements were used to investigate interparticle interactions in concentrated dispersions of the PLA-PEG nanoparticles. This approach has not previously been used to study how the interactions in dispersions of micellar-like assemblies depend on the copolymer geometry. When the volume fraction of the dispersions, score, was increased, the storage modulus, G', became greater than the loss modulus, G, indicating steric interaction between the PEG chains. At higher Φ c o r e values, compression of the grafted polymer chains was observed. The critical volume fraction at which overlap of the PEG chains commences, Φ c o r e crit (i.e., G' = G), was used in conjunction with the overall hydrodynamic radius to determine the grafted PEG chain layer thickness. Micellar-like nanoparticles assembled from a PLA-PEG copolymer with a 5 kDa PEG block and a relatively low molecular weight 3 kDa PLA chain had an appreciable steric layer thickness of 6.3 nm. Hence, interparticle interactions in the concentrated dispersion were soft in nature as a result of the long-range interactions, as shown by the weak scaling dependence of the storage modulus on the volume fraction. The layer became more extended as the molecular weight of the PLA block was increased from 3 to 6 kDa, and as a consequence the PEG chains became less compressible. By using this method to characterize the PEG layer, it should be possible to rationalize the in vivo performance of the PLA-PEG nanoparticles and therefore aid the design of particulate drug carriers.