The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell toxicity than the free DOX at the same concentration after 24 h of treatment. The results suggest the cationic Arg-Leu PEUU NPs could potentially be a useful carrier family for hydrophobic anticancer drugs and produce a synergistic effect between DOX cytotoxicity and the production of TNF-α and NO by macrophages.

Crosslinking of ultra-high molecular weight polyethylene (UHMWPE) has been successfully used to improve its wear performance. Wear is a surface phenomenon and limiting crosslinking to a layer only on the surface is desirable, as crosslinking of the bulk of the implant reduces its mechanical strength and toughness. We present a novel technique to surface crosslink consolidated UHMWPE/vitamin-E blends by diffusing an organic peroxide into the polymer at moderate temperatures, followed by heating to above the peroxide decomposition temperature to cause crosslinking on the surface. We characterized the surface crosslink density and wear rate of surface crosslinked UHMWPE/vitamin-E blends with two different types of peroxides. Both peroxides resulted in surface crosslinking with an increase in wear resistance comparable to the state-of-the-art highly crosslinked UHMWPE used for orthopedic implants. The addition of the antioxidant vitamin-E led to higher oxidation resistance. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2551-2556, 2017.

Radiation cross‐linked ultra‐high‐molecular‐weight polyethylenes (UHMWPEs) are clinically used extensively in total joint arthroplasty due to their high wear resistance. Peroxide cross‐linking of UHMWPE has been proposed to achieve this high level of wear resistance by simultaneously consolidating and cross‐linking in the melt state. High temperature melting of uncross‐linked and cross‐linked UHMWPEs have further shown to improve the toughness. Here, we report on the wear and mechanical properties of a peroxide cross‐linked and high‐temperature melted UHMWPE as a function of vitamin E concentration for oxidative stabilization, peroxide concentration for cross‐linking and high temperature melting temperature for toughness improvement. This method, combining consolidation and cross‐linking in one step, presents an opportunity to manufacture highly wear and oxidation‐resistant joint implant‐bearing surfaces with much improved toughness. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2182–2188, 2019

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