? ? Colorectal cancer (CRC) is the second most common cause of cancer death in the United States with more than 56,000 deaths reported each year. While surgery and chemotherapy have been the major disease intervention methods, chemoprevention has emerged as an alternative to diagnosis and treatment, as evidence of the ability of chemopreventive agents to prevent CRC becomes available. Among agents being tested using preclinical and clinical models, aspirin, calcium and folic acid have received significant attention. All of these agents have shown effects in reducing CRC, when used individually. However, several studies have reported severe side effects, especially for aspirin, including gastrointestinal bleeding and platelet dysfunction associated with high doses needed for chemoprevention. The interest in combination therapy has been increasing, as other promising chemopreventive agents have shown synergistic efficacy with minimized toxicity. Research in combination therapy is still in its infancy; hence more efforts in this area are warranted. The selection of an appropriate drug delivery system is also of importance to ensure that drug reaches its intended site of action. Delivering combinations of chemopreventive agents using a targeted system directly into the local colonic environment would result in lower doses with lesser chances of toxic effects, while maintaining efficacy. The potential benefits of using such carrier systems is apparent, however its application in chemoprevention has never been studied, demonstrating a need for research in this area. Thus, the overall goal of this pilot study is to develop an effective novel combination of chemopreventive agents delivered using a unique nanotechnology- based colon-targeting delivery system to prevent CRC.
The specific aims of our application are : (1) to design and prepare a novel nanotechnology-based drug delivery system capable of encapsulating and delivering predetermined combinations of aspirin, calcium and folic acid directly into the colon; (2) to evaluate the prepared nanoparticle formulations in terms of drug targeting to the colon, bioadhesion to the colonic wall and drug release; (3) to assess the synergistic chemopreventive effects of a combination of aspirin, calcium and folic acid against CRC while minimizing toxic side effects, using an animal model. ? ? ?
| Chaudhary, Abhishek; Sutaria, Dhruvitkumar; Huang, Ying et al. (2011) Chemoprevention of colon cancer in a rat carcinogenesis model using a novel nanotechnology-based combined treatment system. Cancer Prev Res (Phila) 4:1655-64 |
| Kanthamneni, Naveen; Chaudhary, Abhishek; Wang, Jeffrey et al. (2010) Nanoparticulate delivery of novel drug combination regimens for the chemoprevention of colon cancer. Int J Oncol 37:177-85 |
| Chaudhary, Abhishek; Wang, Jeffrey; Prabhu, Sunil (2010) Development and validation of a high-performance liquid chromatography method for the simultaneous determination of aspirin and folic acid from nano-particulate systems. Biomed Chromatogr 24:919-25 |
