title: Chemoprevention of colon cancer in a rat carcinogenesis model using a novel nanotechnology-based combined treatment system.
abstract: Colorectal cancer (CRC) is the third most common cause of cancer death in the United States, accounting for approximately 51,000 deaths each year. We have previously shown in vitro chemopreventive effects of mixtures of aspirin, folic acid, and calcium (AFAC) on colon cancer cell lines. The objective of the present study was to evaluate the in vivo effects of orally administered, colon targeted chemopreventive combination regimens on the inhibition of aberrant crypt foci (ACF) in a rat model of colon carcinogenesis using (i) unmodified (free drug) combinations of AFAC and (ii) nanoparticle-encapsulated combinations of the same agents. A 14-week animal study was conducted in three phases to determine an optimal effective dose from AFAC combinations and evaluate the efficacy of nanotechnology-based chemopreventive regimens administered in combined (mixtures) and individual (single entity) forms. ACF inhibition when compared with azoxymethane-treated rat control group was significant in both the unmodified and the modified nanoparticle-mediated chemopreventive regimens, showing a range of 31% to 38% (P < 0.05) and 50% to 75% (P < 0.001) reduction, respectively, in the number of ACFs. In addition, the nanoparticulate combination regimens of AFAC showed a 2-fold increase in suppression of ACF compared with free drug mixtures. Individual administration of nanoparticle-encapsulated drugs showed no significant effect on the reduction of ACF. Histochemical analysis provided further confirmation of chemopreventive effects, showing a significant reduction in cell nuclear proliferation. Overall, our results provide a strong proof of concept using nanoparticle-mediated combination treatment in the chemoprevention of colon cancer.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Dhruvitkumar
authors.initials: D
authors.lastname: Sutaria
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wang
authors.forename: Sunil
authors.initials: S
authors.lastname: Prabhu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001241:Aspirin / Q000627:therapeutic use*; D001397:Azoxymethane / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000627:therapeutic use*; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014803:Vitamin B Complex; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005492:Folic Acid; D001397:Azoxymethane; D001241:Aspirin