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.

Hyaluronan–cisplatin conjugate nanoparticles embedded in Eudragit S100-coated pectin/alginate microbeads for colon drug delivery

“…19 The size of the resulting HCNPs, as measured by dynamic light scattering, averaged 171.10 ± 48.58 nm. The polydispersity index was 0.67.…”

“…Thakral et al used the natural polymer as a core and subsequently coated it with Eudragit S100 for colon targeting. 18,19 In our previous work, we successfully fabricated Eudragit S100-coated pectinate/alginate microspheres (PAMs) using an electrospray method and polyelectrolyte multilayer-coating technique in an aqueous solution, and demonstrated that cisplatin release from Eudragit S100-coated PAMs was retarded in simulated gastric conditions. 20 However, the new drug-delivery system only improved the efficiency of protecting drug activity.…”

Soluplus-Solubilized Citrated Camptothecin—A Potential Drug Delivery Strategy in Colon Cancer

“…The specific pH conditions of the colonic region were exploited to deliver the drug to the region, by developing a pHdependent system, using Eudragit S100 (22). Eudragit S100 is an anionic polymer synthesized from methacrylic acid and methyl methacrylate which dissolves in the region of the digestive tract where pH is >7 (23,24). The system was designed in such a manner that an acidic microenvironment is developed in colon after the release of the drug from the system, to arrest the hydrolysis of the lactone ring of CPT.…”

Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

“…3 Similar observations have also been made in the management of colon cancer. 4,5 In fact, the deposition and adherence of fluorescent polystyrene particles were greater in the ulcerated regions of the inflamed tissue than in nonulcerated control tissue in experimental models of rodent colitis; this adhesion was size-dependent, the best results being obtained with particle sizes ranging from 25 to 100 nm. 3 Based on this paradigm, different groups have developed the delivery of several drugs, such as tacrolimus and rolipram, delivered on poly(lactic-co-glycolic acid) nanoparticles; dexamethasone on poly(d-lactide) particles; 3 or fluticasone propionate on hydroxypropyl betacyclodextrin.…”