Inhalable Fucoidan Microparticles Combining Two Antitubercular Drugs with Potential Application in Pulmonary Tuberculosis Therapy

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.

Hydrothermal Processing of Laminaria ochroleuca for the Production of Crude Extracts Used to Formulate Polymeric Nanoparticles

“…The authors of this paper have reported an application of fucoidan as a matrix material of inhalable microparticles, associating two first-line antitubercular drugs, in a strategy of inhalable tuberculosis therapy. Fucoidan microparticles have shown ability to undergo internalisation by alveolar macrophages and activate the target cells [18,19].…”

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties

“…The mass of the particles with a diameter of less than 5 µm can be calculated (this mass otherwise corresponds to the fine particle dose if divided by the number of the applied DPI capsules). A FPF < 5 µm can be obtained from the graph as a percentage of the ED [60]. From the percentage value for 3 µm ( Figure A1, blue line) we can get the mass of the particles with a diameter less than 3 µm, from which we get FPF < 3 µm as a percentage of the ED.…”

“…The amounts filled into the capsules were calculated, the MXP content per sample was 1.3 mg [43]. By the investigation, two cycles of inhalation were applied for 4 s. Breezhaler ® (Novartis International AG, Basel, Switzerland) was used as a DPI device with three [60] transparent, size 3 hard gelatin capsules (Coni-Snap ® , Capsugel, Bornem, Belgium). The applied DPI device, the capsules, the mouthpiece, the induction port, the eight plates of the ACI, and the filter were washed with methanol + pH 7.4 phosphate buffer (60 + 40 v/v%).…”

Inhalable Spray-Dried Chondroitin Sulphate Microparticles: Effect of Different Solvents on Particle Properties and Drug Activity

“…The comparison of release profiles supports the conclusion that the matrix rules the release pattern. Although ChS is a hydrophilic polymer, it was able to provide a slower release of these drugs in comparison with microparticles composed of fucoidan, another hydrophilic polymer, which has shown a total release of INH and RFB in 30 min [33]. Locust bean gum, in turn, provides more viscous solutions and, thus, sustained the release of INH until 120 min and RFB up to 240 min [34], while low molecular weight chitosan microparticles released completely INH and RFB in 120 min [35].…”