Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon

Abstract

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

In vitrocytotoxicity andin vivoefficacy of 5-fluorouracil-loaded enteric-coated PEG-crosslinked chitosan microspheres in colorectal cancer therapy in rats

“…treatment because of its side effects and patient compliance. In this pursuit, numerous efforts have been made to target drugs to colon such as prodrugs, pHdependent and time release systems, microflora-activated systems, intestinal-pressure colon delivery capsules, etc (Torchillin, 1998;Yang et al, 2002;Chourasia & Jain, 2004a,b;Torchillin, 2007;Ghorab et al, 2011;Ramasamy et al, 2013;Rai et al, 2014;Sareen et al, 2014;Zeng et al, 2015). The wide pH range of gastrointestinal (GI) tract poses a challenge for the delivery of drug to the colon and hostile environment of the stomach become ineffective due the failure of a delivery device.…”

“…The wide pH range of gastrointestinal (GI) tract poses a challenge for the delivery of drug to the colon and hostile environment of the stomach become ineffective due the failure of a delivery device. To overcome this problem, enteric coating of the device matrix has been attempted (Ghorab et al, 2011;Rai et al, 2014;Sareen et al, 2014;Zeng et al, 2015).…”

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone

“…They can be categorized as: (a) Prodrug approach (Riley & Turnberg, 1990;McLeod et al, 1994); (b) Pressure-based systems (Muraoka et al, 1998;Jeong et al, 2001); (c) The temporal control of delivery (Steed et al, 1997;Del Curto et al, 2009); (d) pH-based systems (Klein et al, 2005;Basak & Adhikari, 2009;Sareen et al, 2014), and (e) Enzyme-based systems (Xi et al, 2005;Varshosaz et al, 2006;Kshirsagar et al, 2011;Ramasamy et al, 2013;Rai et al, 2014). Polysaccharides which undergo hydrolysis of their glycosidic bonds by the microflora of the colon appear to be the most promising because of their attractive properties, such as wide availability, low cost of production, low toxicity and biodegradability (Chourasia & Jain, 2004).…”

“Colon Targeted Delivery System (Codestm): Propitious Approach in Targeting Colon”

“…Barrier layer prevents possible interaction between cationic and anionic polymer coatings. [14] The polysaccharide in the core of the tablet dissolves and diffuses out as soon as the system reaches colon. [10] The existing microflora in the colon will enzymatically (β-galactosidase)…”