Title : The role of cellulose nanofibers on colon-specific microparticles to target 5-Aminosalicylic acid to treat inflammatory bowel disease
Inflammatory bowel diseases (IBD) are considered a set of autoimmune disorders characterized by chronic inflammation, mucosal ulcerations, and haemorrhage of the gastrointestinal tract (GIT). 5-Aminosalicylic acid (5-ASA) is the drug of choice in the treatment of mild to moderate IBD. For this drug to exert a pronounced therapeutic effect, it is necessary to avoid the release in the upper portions of the GIT and promote its release in the colonic region, which contributes to a localized treatment with a significant reduction of side effects. The development of systems employing biodegradable polysaccharides by enzymes secreted by the colonic microbiota has been considered the most reliable way to release drugs in the colon. In this scenario, retrograded starch (RS), a fraction of starch that escapes of digestion in the stomach and small intestine, along with pectin (P), have been considered promising candidates for the building of colonic systems. However, the high hydrophilicity of these polymers remains as an important challenge to be overcome and the use of cellulose nanofibers (CNF) as reinforcement can be considered a suitable tool in the optimization of the RS/P excipient. Given the above, this work aims to develop bioresponsive microparticles from the optimized excipient RS/P/CNF for targeting 5-ASA to the colon in the treatment of IBD. 5-ASA-loaded RS/P microparticles containing CNF (10 %, 25 % and 50 %) were prepared by spray drying technique and submitted to tests of in vitro cytotoxicity, ex vivo mucoadhesion, intestinal permeation on Caco-2 cells monolayers, and in vitro drug release. Results showed that microparticles were biocompatible at all analysed concentrations (0.0625-2.0000 mg/mL). Increasing concentrations of CNF were responsible for the improvement of mucoadhesion, analysed in ileocolonic sections of pigs, which reached 3.4 N of mucoadhesive force for the sample containing the highest concentration of CNF (50 %). Intestinal permeability revealed that the microparticles increased the permeation of 5-ASA by up to 10 times, which ranged from 29 to 48 % and can be attributed to the action of the RS/P blend in the opening of the paracellular junctions. In addition, the sample with an intermediate concentration of CNF (25 %) promoted the highest permeation, which may be related with the greatest release rates of 5-ASA in simulated colonic medium. Considering that spray-drying is a scalable process widely used by the pharmaceutical industry, the results obtained indicate the potential of CNF for optimizing RS/P microparticles intended to release 5-ASA in the distal parts of the GIT affected by IBD.
Audience Take Away:
- The use of biodegradable polysaccharides and nanoreinforcement to build colon-specific drug delivery.
- The rational selection of type of polymer and its concentrations modulates the physical-chemical and biological properties of the drug delivery systems.
- Colonic systems are widely employed to treat local and systemic diseases.
- Rational thinking in design of new delivery systems can simplify the Research and Development job.
- Rational selection of different polymer concentrations can meet specific needs.