Abstract
The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6–3.9 µm. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.
Highlights
Tuberculosis (TB) is a leading infectious cause of death worldwide, even though a vaccine and several effective antibiotics are available for its prevention and treatment
Spray-dried FUC microparticles loaded with a combination of two first-line antitubercular drugs (INH and RFB) were produced with a yield around 81%, indicating the effectiveness of the process
Inhalable dry powders based on FUC were produced to associate two first-line antitubercular drugs (INH and RFB) in a single formulation
Summary
Tuberculosis (TB) is a leading infectious cause of death worldwide, even though a vaccine and several effective antibiotics are available for its prevention and treatment. Global TB control is very difficult due to many factors, including late diagnosis and patient nonadherence to long-term treatments, which leads to a high incidence of extensive resistance to effective antitubercular drugs [2]. The current therapy faces serious challenges, such as multi-drug interactions—especially with antiretroviral agents in cases of TB and HIV co-infection—long-term treatment, and antibiotic toxicity, which lead to adverse effects, Polymers 2018, 10, 636; doi:10.3390/polym10060636 www.mdpi.com/journal/polymers. TB therapy, in addition to patient adherence to the treatment and re-examination to verify the therapy, in addition to patient adherence to the treatment and re-examination development to verify the ofdevelopment the active form of the disease.
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