Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer

Abstract

5-Fluorouracil is used in the treatment of colorectal cancer along with oxaliplatin as first line treatment, but it is having lack of site specificity and poor therapeutic effect. Also toxic effects to healthy cells and unavailability of major proportion of drug at the colon region remain as limitations. Toxic effects prevention and drug localization at colon area was achieved by preparing enteric-coated chitosan polymeric nanoparticles as it can be delivered directly to large bowel. Enteric coating helps in preventing the drug degradation at gastric pH. So the main objective was to prepare chitosan polymeric nanoparticles by solvent evaporation emulsification method by using different ratios of polymer (1:1, 1:2, 1:3, 1:4). Optimized polymer ratio was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), entrapment efficiency and particle size and further subjected to enteric coating. In vitro drug release studies were done using dialysis bag technique using simulated fluids at various pH (1.2, 4.5, 7.5, 7.0) to mimic the GIT tract. 5-FU nanoparticles with drug: polymer ratio of 1:2 and 1:3 has shown better particle size (149 ± 1.28 nm and 138 ± 1.01 nm respectively), entrapment efficiency (48.12 ± 0.08% and 69.18 ± 1.89 respectively). 5-FU E1 has shown better drug release after 4 h and has shown 82% drug release till 24 h in a sustained manner comparable to the non-enteric coated tablets, which released more than 50% of the drug before entering the colon region. So we can conclude that nanoparticles prepared by this method using the same polymer with the optimized ratio can represent as potential drug delivery approach for effective delivery of the active pharmaceutical ingredient to the colorectal tumors.

5-Fluorouracil enteric-coated nanoparticles for improved apoptotic activity and therapeutic index in treating colorectal cancer

“…In vitro drug release for 5-FUEC in various simulated fluids representing GIT pH had conformed its stability in acidic pH and there after releasing the drug in the basic pH. Drug release was found to be only after 4 h once it enters the intestinal fluid and was localized along with its sustained release over a period of 24 h (Tummala et al, 2015b). In this study, extensive cellular and apoptotic studies were carried out to investigate the apoptotic activity of the 5-FUEC using Annexin-PI assay (using flow cytometry) and Acridineorange/Ethidium bromide method.…”

“…We emphasized mainly on the localization of the drug in the target area, thereby minimizing the chances of drug distribution to the other organs in our previous studies (Tummala et al, 2015b). Essentially, coating of anti-neoplastics with polymers comprising of the classes like cellulose derivatives (Levine et al, 1987), acrylic polymers (Rasmussen et al, 1982) etc., that can deliver major amount of the drug directly to the large bowel thereby bypassing the systemic circulation can be explored.…”

Recent insights into nanotechnology development for detection and treatment of colorectal cancer

“…49 In another study, researchers prepared chitosan polymeric NPs by the solvent evaporation emulsification method, with varied ratios of polymer. 50 They concluded that the NPs prepared by solvent evaporation emulsification using the polymer at the optimum ratio represents an approach for potentially successful delivery of the active pharmaceutical element to the colorectal tumors. 50 Total health centre complex N-38 is a highly effective drug against many cancers, as it contains pharmaceutically active ingredients.…”

“…50 They concluded that the NPs prepared by solvent evaporation emulsification using the polymer at the optimum ratio represents an approach for potentially successful delivery of the active pharmaceutical element to the colorectal tumors. 50 Total health centre complex N-38 is a highly effective drug against many cancers, as it contains pharmaceutically active ingredients. However, the development of an optimal delivery system for SN-38 is challenging, owing to its low solubility and the presence of a labile lactone ring.…”

Formulation and Optimization of Controlled Release 5-Fluorouracil Tablets for Colonic Delivery

“…Enteric coated dosage forms for the drug, like matrix tablets, microspheres or nanoparticles using polymers like Eudragit S100 or ethylcellulose have been used for such purposes. [6][7][8][9] Besides, novel drug delivery systems like modified pulsincap delivery, polyelectrolyte complexes, osmotic devices, etc were also tried out. [10][11][12] The answer to the second question may be determined by analysing available literature of drug dosing and pharmacokinetic data.…”