title: The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres.
abstract: The aim of the present study was to prepare valdecoxib, a cyclo-oxygenase-2 enzyme inhibitor, as a loaded multiparticulate system to achieve site-specific drug delivery to colorectal tumors. Film coating was done with the pH-sensitive polymer Eudragit S100 and sodium alginate was used as mucoadhesive polymer in the core. The microspheres were characterized by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy and were evaluated for particle size, drug load, in vitro drug release, release kinetics, accelerated stability, and extent of mucoadhesion. The coated microspheres released the drug at pH 7.4, the putative parameter for colonic delivery. When applied to the mucosal surface of freshly excised goat colon, microspheres pretreated with phosphate buffer pH 7.4 for 30 minutes showed mucoadhesion. To ascertain the effect of valdecoxib on the viability of Caco-2 cells, the 3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide) test was conducted using both valdecoxib and coated microspheres. In both cases, the percentage of dehydrogenase activity indicated a lack of toxicity against Caco-2 cells in the tested concentration range. Drug transport studies of the drug as well as the coated microspheres in buffers of pH 6 and 7.4 across Caco-2 cell monolayers were conducted. The microspheres were found to exhibit slower and delayed drug release and lower intracellular concentration of valdecoxib.
authors: Centre for Biomedical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India.
authors: Naveen K
authors: NK
authors: Thakral
authors: Alok R
authors: AR
authors: Ray
authors: Daniel
authors: D
authors: Bar-Shalom
authors: André Huss
authors: AH
authors: Eriksson
authors: Dipak K
authors: DK
authors: Majumdar
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D003110:Colonic Neoplasms / Q000188:drug therapy*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006041:Goats; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D007420:Intestine, Large / Q000378:metabolism; D007555:Isoxazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010088:Oxidoreductases / Q000378:metabolism; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014961:X-Ray Diffraction; D000096926:Benzenesulfonamides
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007555:Isoxazoles; D010088:Oxidoreductases; D011109:Polymethacrylic Acids; D013449:Sulfonamides; C038300:methylmethacrylate-methacrylic acid copolymer; C406224:valdecoxib; D000096926:Benzenesulfonamides