Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

A infecção causada pelo Helicobacter pylori tem sido associado a várias doenças gástricas, inclusive o câncer gástrico. Esta bactéria coloniza a mucosa gástrica de metade da população do mundo, e os tratamentos disponíveis são mal sucedidos em praticamente um em cada cinco pacientes. Polímeros mucoadesivos, tais como quitosana, são usados como sistemas de liberação gástricos para uma melhor liberação do fármaco nos locais de atuação. Neste trabalho, partículas de quitosana contendo amoxicilina foram obtidas pelo método de coacervação/precipitação visando uma liberação controlada do fármaco no ambiente do estômago, no intuito de melhorar a eficácia terapêutica da amoxicilina no tratamento do Helicobacter pylori. A incorporação da amoxicilina foi feita utilizando duas técnicas diferentes: durante a formação das partículas e por adsorção das partículas formadas .As partículas foram caracterizadas quanto ao tamanho médio, potencial zeta, DSC, FTIR, eficiência de encapsulação e liberação in vitro em HCl 0,1N. As partículas apresentaram uma eficiência de encapsulação de 83%, tamanho médio de partícula nanométrica e potencial zeta positivo (20 mV). A amoxicilina encapsulada nas micropartículas teve liberação in vitro de apenas 40 % em 120 minutos. The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.