title: A nanomedicine-promising approach to provide an appropriate colon-targeted drug delivery system for 5-fluorouracil.
abstract: Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics), and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Sima
authors.initials: S
authors.lastname: Singh
authors.affiliation: Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India.
authors.forename: Niranjan G
authors.initials: NG
authors.lastname: Kotla
authors.affiliation: Department of Pharmaceutics, Ram Gopal College of Pharmacy, Rohtak, Haryana, India.
authors.forename: Sonia
authors.initials: S
authors.lastname: Tomar
authors.affiliation: Department of Pharmaceutics, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, India.
authors.forename: Balaji
authors.initials: B
authors.lastname: Maddiboyina
authors.affiliation: Department of Chemical Engineering, Northeastern University, Boston, MA, USA ; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
authors.affiliation: Ranbaxy Laboratory Ltd, Gurgaon, Haryana, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India.
authors.forename: Omprakash
authors.initials: O
authors.lastname: Sunnapu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002432:Cecum / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003967:Diarrhea / Q000175:diagnosis; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D017208:Rats, Wistar
chemical_list: D005472:Fluorouracil
keywords: 5-fluorouracil; colon-specific drug delivery system; polymeric nanoparticles; probiotics