title: Optimization of chitosan nanoparticles for colon tumors using experimental design methodology.
abstract: Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.
authors.affiliation: a Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour Central University , Sagar , MP , India.
authors.forename: Anekant
authors.initials: A
authors.lastname: Jain
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Jain
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D048271:Chitosan; D005472:Fluorouracil
keywords: 5FU; Chitosan nanoparticles; colon targeted drug delivery; colon tumors; parametric optimization; response surface methodology