Investigation of the therapeutic efficacy of codelivery of psiRNA-vascular endothelial growth factor and pIL-4 into chitosan nanoparticles in the breast tumor model.

Angiogenesis has been known to increase tumor growth and for its metastatic potential in human tumors. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is a promising therapeutic target for breast cancer. VEGF is an essential target for RNAi-based gene therapy of breast cancer. Interleukin-4 (IL-4) may act as an anti-angiogenic molecule that inhibits tumor growth and migration in rats. The purpose of the present study was to improve therapeutic efficacy in breast cancer with the codelivery of siRNA-expressing plasmid targeting VEGF and IL-4-expressing plasmid encapsulating into chitosan nanoparticles (NPs). The codelivery of psiVEGF and pIL-4 plasmids greatly enhanced in vitro and in vivo gene-silencing efficiency. For the in vitro study, when psiVEGF and pIL-4 into chitosan NPs were combined (81%), the gene-silencing effect was higher than psiVEGF and pIL-4 NPs alone. The in vivo study breast tumor model demonstrated that the administration of coencapsulation of psiVEGF and pIL-4 into chitosan NPs caused an additive effect on breast tumor growth inhibition (97%), compared with containing NPs psiVEGF or pIL-4 alone. These results indicate that chitosan NPs can be effectively used for the codelivery of pIL-4 and siVEGF-expressing plasmid in a combination therapy against breast cancer.

Chemical delay: an alternative to surgical delay experimental study.

The delay phenomenon has long been recognized as a powerful adjunct to flap surgery. Currently, delay procedures remain a reliable method of maximizing flap survival. Although delay yields successful results, the necessity of an additional surgical procedure is a persistent disadvantage from both clinical and economic perspectives. The authors' purpose is to demonstrate the usefulness of a novel chemical delay technique that obviates the need for a surgical delay procedure. This technique contains an epinephrine-loaded microsphere delivery system. In this study, 30 rats were subdivided into three groups of 10 animals. In group I, transverse rectus abdominis musculocutaneous (TRAM) flaps were delayed surgically 1 week before formal elevation. Group II (sham chemical delay) animals were injected with saline-loaded microspheres into the entire undersurface of the proposed TRAM flaps, which were elevated 1 week later. In group III rats, epinephrine-loaded microspheres were injected into the undersurface of the TRAM flaps to initiate a chemical delay 1 week before surgical elevation. Groups were compared via TRAM flaps 1 week after elevation. There was a significant difference between groups I and III in favor of surface area viability and angiographic assessment (p < 0.05). Surgical delay has traditionally been accepted to be the most reliable method of enhancing flap viability. Statistically similar results were obtained by chemical delay initiated by epinephrine-loaded microspheres. Chemical delay is less invasive, less time-consuming, and far more cost-effective compared with its surgical alternative. The chemical delay model lends further support to the role of relative hypoxia as the primary promoter of the delay phenomenon.