Micropartículas de quitosana como sistema de liberação colônica de mesalazina no tratamento da doença inflamatória intestinal

Abstract

In IBD, gastrointestinal tract is partially or completely affected by two main conditions, Ulcerative Colitis and Crohn’s Disease, chronic and idiopathic diseases. First line treatment includes anti-inflammatory drugs as mesalazine by oral or rectal administration. Main treatment limitation is related to drug delivery system, since it should reach colonic tissue and afford an optimum level of mesalazine in that area of TGI, without contributing to previous drug delivery. Low drug solubility is also a complicating factor at local delivery in colon. Microparticles can allow drug delivery vectorization, because they can be captured by immune system cells and targeted to inflammation site. In this study, chitosan microparticles were produced using different methods and conditions. Three techniques were applied: polyelectrolyte complexation with hydroxypropylmethylcellulose phthalate; chemical crosslinking with genipin; and emulsification combined with chemical crosslinking with genipin. Samples with microparticles were analyzed for size, zeta potential, powder x-ray diffraction and infrared spectroscopy, and then, drug release profiles were analyzed at colonic and gastric pH. Nanoparticles without drug could be made using first method (491 nm, PdI=0.26 and ζ= 23.2), but we could not produce stable particles with mesalazine. Microparticles produced by second method showed degradation. Sub-micron and microparticles could be produced by emulsification and chemical crosslinking with genipin method (2692 nm, PdI=0.6 and ζ= 46). Mild agitation at 800 rpm for 3 hours has been produced bigger particles and with more spherical shape than using more strong agitation at 8,000 rpm for 5 minutes. Yield found was about 50%, and it was considered satisfactory, since faced difficulties to prepare a polymeric matrix containing the drug applying other techniques. Samples crystalline structure has been checked by powder ray-x diffraction, while covalent bound between chitosan and genipin could be showed by infrared spectroscopy. It was obtained a sigmoidal drug release profile from microparticles produced by third method, what it means that a slower drug delivery in the beginning, followed by a fast release, and it could represent a colon targeted release.