Microencapsulation of antitubercular drugs in a matrix of partially hydrolyzed guar gum, for application in tuberculosis treatment

Abstract

Trabalho realizado na Universidade do AlgarveTuberculosis (TB), despite being a completely curable disease, has reemerged due to drug resistance and deadly synergism with HIV infection, which limit the success of its management. Lung tuberculosis is the main manifestation of TB. Thus, exploring the inhalable route for a local delivery of antitubercular drugs seems a promising therapeutic approach. Partially hydrolyzed guar gum (PHGG) is a strong candidate as matrix material for antitubercular drug carriers. This is mainly due to its affinity for macrophages, the hosts of mycobacteria, which is mediated by the binding of sugar units to macrophage surface receptors. In this work, PHGG-based microparticle formulations were produced by spray-drying, evaluated for cristallinity pattern (X-ray diffraction) and ability for drug association, and in vitro drug release profiles were determined. The cytotoxicity of microparticles was also evaluated (MTT and LDH release assays). Additionally, the therapeutic effect of drug-loaded microparticles was evaluated in vitro on macrophage-like cells infected with mycobacteria strains. The results showed that microparticles exhibited suitable properties for pulmonary delivery (aerodynamic diameter between 1 and 3 μm). A favorable cytotoxic profile was evidenced, as no overt toxicity was detected in representative respiratory cell lines (A549 and Calu-3 cells), although a mild toxic effect was observed in macrophage-like cells. The in vitro response of infected macrophages to drug-loaded PHGG microparticles was considered promising, as only 20% of mycobacteria remained viable upon a single treatment with microparticles. This thesis addresses macrophages as therapeutic target, unraveling the unique role of polysaccharides on pulmonary drug delivery in the ambit of tuberculosis therapy.info:eu-repo/semantics/publishedVersio