AAPS NERDG Awards Writeup
Three Pharmaceutical Sciences Doctoral Students Receive the 2012 AAPS-NERDG Academic Research Awards
During the 2012 annual meeting of American Association of Pharmaceutical Scientists Northeast Regional Discussion Group (AAPS-NERDG) annual meeting in Rocky Hill, CT, three doctoral students, Sean Essex, Jing Xu and Namita Dodwadkar, from our department have received the first place, second place and third place, respectively, in Academic Research Awards Podium sessions.
Sean Essex is a Ph.D student in Distinguished Professor Vladimir Torchilin’s lab in the Center for Pharmaceutical Biotechnology and Nanomedicine. His project is entitled “Poly(ethylenimine) Based Nanocarrier Improves Systemic Tumoral Delivery of siRNA”. Effectiveness of systemic siRNA therapies for cancer treatment is limited by a poor tumoral uptake and low stability in blood of siRNA upon intravenous injection. In order to overcome these difficulties, they developed a nanocarrier based on phospholipid-modified polyethylenimine (PEI-PE) and phospholipid-modified polyethylenglycol (PEG-PE) for the systemic tumoral delivery of siRNA. In such carrier, PEI-PE is expected to provide effective condensation and intracellular delivery of siRNA (previously shown by our group Navarro et al., Nanomedicine, 2011) while PEG-PE is thought to reduce the association of the carrier with plasma proteins and non-specific tissues upon intravenous injection. To confirm this, a biodistribution study was carried out in tumor-bearing mice using fluorescein dye-labeled siRNA (FL-siRNA) injected in the naked form or complexed with non-modified PEI, PEI-PE or PEI-PE/PEG-PE mixtures (1:10 w/w). The protective effect of PEG-PE in the carrier was confirmed by improved blood stability and significantly higher accumulation of the siRNA loaded in the PEI-PE/PEG-PE carrier, at the tumor site.
Jing Xu is a doctoral candidate working in the laboratory of Distinguished Professor and Chair Mansoor Amiji, and her doctoral thesis research project is titled "Multimodal Therapeutic Approach for Pancreatic Cancer: Delivery of Combination wt-p53 Gene and Gemcitabine in Epidermal Growth Factor Receptor-Targeted Gelatin Nanoparticles”. She has showed in her preliminary studies that both control and EGFR targeted thiolated gelatin nanoparticles can efficiently encapsulate plasmid DNA and preserve plasmid structure, protect them during intracellular transport. This system successfully transfected Panc-1 cells with therapeutic plasmid, which encoded wild type p53 protein and triggered apoptosis in pancreatic cancer cells. To further enhance the efficiency of the treatment, she has included gemcitabine into the gelatin nanoparticle system. Cytotoxicity studies have also shown that EGFR-targeted nanoparticles significantly enhance the toxicity of gemcitabine. Their studies have suggested that EGFR-targeted thiolated gelatin nanoparticles can serve as a safe and efficient DNA and drug delivery system as a treatment for pancreatic cancer. The ongoing efforts in this project will focus on the evaluation of the combination treatment with drug and gene therapy, in vivo anti-tumor activity using a subcutaneous and orthotopic Panc-1 tumor model in immune-compromised nude mouse.
Namita Dodwadkar is a doctoral candidate in Distinguished Professor Vladimir Torchilin's laboratory in the Center for Pharmaceutical Biotechnology and Nanomedicine. Ms. Dodwadkar’s project is entitled “Surface Conjugation of Triphenylphosphonium Targets Poly(amidoamine) Dendrimers to Mitochondria” Dendrimers are hyperbranched, monodisperse, tree-like synthetic macromolecules with three distinct components that include a central core, repeated branches and a large number of functional groups on the surface. Since their discovery, dendrimers have been studied extensively and hold great promise as a nanocarrier for site-specific delivery of therapeutic and imaging agents. With the ever increasing evidence that mitochondrial dysfunction contributes to a variety of human disorders including neurodegenerative and neuromuscular diseases, diabetes, obesity and cancer, this study aimed at developing a novel mitochondria-targeted dendrimer. They believe that such a mitochondria-targeted dendrimer-based nanocarrier could be useful for imaging as well as for selective delivery of bio-actives to the mitochondria for the treatment of diseases associated with mitochondrial dysfunction.