The results shown in this study are promising and set a platform for further examining the suitability of this PEI-enhanced delivery system in vivo. Acknowledgments This work is supported by a research Grant to S. Prakash from Canadian Institutes of Health Research (CIHR) (MOP 93641). S. Abbasi is supported by the McGill Faculty of Medicine Internal Studentship—G. G. Harris Fellowship Inhibitors,research,lifescience,medical and the Ontario-Quebec Exchange Fellowship. A. Paul acknowledges the financial support from NSERC Alexander Graham Bell Canada Graduate Scholarship. The authors are grateful for the assistance
provided for TEM imaging by Dr. Xue-Dong Liu, McGill, Department of Physics.
It was estimated that there were 1,500,000 new BI6727 cancer cases and approximately Inhibitors,research,lifescience,medical 560,000 deaths out of cancer in 2009 [1]. Chemotherapy is an important treatment option for patients with cancer, however chemotherapy drugs suffer from numerous problems including nonspecific uptake by healthy tissue, poor circulation times, and suboptimal accumulation in the tumor. Often, a large percentage of cytotoxic drug administered to the
patient does not reach the tumor environment, but rather is distributed throughout the body, resulting in the many toxic effects associated Inhibitors,research,lifescience,medical with chemotherapy and a narrowing of the drug’s therapeutic window. The delivery of chemotherapeutic drugs to tumors is still a major hurdle in the eradication of cancer, and the continual development of drug delivery Inhibitors,research,lifescience,medical technologies is vital to future breakthroughs in chemotherapy. Polymer micelles offer a promising approach to achieving these goals
due to their inherent ability to overcome multiple biological barriers, such as avoidance of the reticuloendothelial system (RES) [2]. Due to their unique size range (20–150nm), Inhibitors,research,lifescience,medical micelles are able to avoid renal clearance (typically less than 20nm) and uptake by the liver and spleen (particles greater than 150nm). These micelles can also preferentially accumulate in solid tumors via the enhanced permeation and retention (EPR) effect [3, 4]. The EPR effect is a consequence of the disorganized nature of the tumor vasculature, which results in increased permeability of polymer therapeutics and drug retention at the tumor site. Endonuclease Due to these promising aspects, a number of groups have developed various polymer micelle motifs, encapsulating a wide range of therapeutic classes [5–17]. Colon cancer is the third most common cancer in men and women in most of the developed world [1]. Irinotecan, a topoisomerase I inhibitor, is approved in the clinic for colorectal cancer first-line therapy in combination with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) regimen or for monotherapy in second-line therapy following a failed FOLFOX regimen [18]. SN-38, the active metabolite of irinotecan, is about 500–1000 times more cytotoxic than irinotecan [18–20].