Development of a Sequential Antibiotic Releasing System for Two-Stage Total Joint Replacement Surgery.

In recent years, there has been an increase in nanoparticle research towards creating better release systems that can maintains the effective dosage over desired periods. Conventional nanoparticle systems have not been successful for this goal. Thus, the aim of this study is to evaluate the sequential release profiles of hybrid materials, combining nanoparticles, hydrogels and bone cement, for the treatment of arthroplasty infections. In this study, Vancomycin, which is one of the most used antibiotics in orthopedics, was loaded to alginate-chitosan nanoparticles. These drug-loaded nanoparticles were dispersed in an alginate gel and the gel covered the polymethylmethacrylate bone cement. After the crosslinking of the gel around the bone cement, the sequential release profile was evaluated for 60 days in vitro. The results of the morphological, chemical characterization and encapsulations studies showed that different loadings of drugs resulted in different encapsulation efficiencies. Although the release profile from the nanoparticles was as expected, the sequential release profile of the combined system has a Fickian type release for a longer time period. In conclusion, the results indicate that combining different release systems can alter the release profile of the system.

Regulation of tumor angiogenesis by EZH2.

Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach.