No abstract

Block copolymers with and without reactive functionalities can improve fracture resistance in brittle epoxies even when added in relatively small amounts (<5 wt %). At certain compositions, amphiphilic block copolymers spontaneously self‐assemble into vesicles, spherical micelles, or wormlike micelles in thermoset resins, and these morphologies are retained with the full curing of the resins. The addition of such block copolymers leaves the glass‐transition temperature of these blends relatively unchanged, whereas the fracture resistance increases up to a factor of 3.5 for the vesicle‐modified blends. For epoxies modified with block copolymers self‐assembled into a spherical geometry (vesicles or spherical micelles), the fracture resistance scales with the ratio of the interparticle distance to the average vesicle (or spherical micelle) diameter (Di/Dp) and increases as this quantity is reduced. Greater adhesion between the vesicle and epoxy resin improves the fracture resistance only at higher values of Di/Dp, at which the materials are more brittle. Debonding and subsequent matrix plastic deformation are identified as the toughening mechanisms in these blends. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2444–2456, 2003

A series of paclitaxel prodrugs designed for formulation in lipophilic nanoparticles are described. The hydrophobicity of paclitaxel was increased by conjugating a succession of increasingly hydrophobic lipid anchors to the drug using succinate or diglycolate cross-linkers. The prodrugs were formulated in well defined block copolymer-stabilized nanoparticles. These nanoparticles were shown to have an elimination half-life of approximately 24 h in vivo. The rate at which the prodrug was released from the nanoparticles could be controlled by adjusting the hydrophobicity of the lipid anchor, resulting in release half-lives ranging from 1 to 24 h. The diglycolate and succinate cross-linked prodrugs were 1-2 orders of magnitude less potent than paclitaxel in vitro. Nanoparticle formulations of the succinate prodrugs showed no evidence of efficacy in HT29 human colorectal tumor xenograph models. Efficacy of diglycolate prodrug nanoparticles increased as the anchor hydrophobicity increased. Long circulating diglycolate prodrug nanoparticles provided significantly enhanced therapeutic activity over commercially formulated paclitaxel at the maximum tolerated dose.

Ostwald ripening, the interfacial-energy-driven dissolution and reprecipitation of solutes, becomes an increasingly significant problem for nanoparticle formulations. We present the first quantitative study of Ostwald ripening for nanoparticle dispersions. The Lifshitz-Slyozov-Wagner (LSW) theory of particle growth driven by diffusion is applied to study beta-carotene nanoparticles with sizes of O(100 nm) formed by our block-copolymer protected Flash Nanoprecipitation process. A numerical implementation of the LSW theory that accounts for the original particle size distribution is presented. The predicted particle sizes from the numerical simulation are compared with the experimental results measured by dynamical light scattering. The results show quantitative agreement with no adjustable parameters. The addition of antisolvent results in the reduction of the ripening rate by dramatically decreasing bulk solubility.