Recent advances in PLGA micro/nanoparticle delivery systems as novel therapeutic approach for drug-resistant tuberculosis.

Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis and is a significant public health concern globally. The World Health Organization (WHO) recommends a combination regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (ETB), to treat tuberculosis. However, these drugs have low plasma concentrations after oral administration and require multiple high doses, which may lead to the occurrence and development of drug-resistant tuberculosis. Micro/Nanotechnology drug delivery systems have considerable potential in treating drug-resistant tuberculosis, allowing the sustained release of the drug and delivery of the drug to a specific target. These system properties could improve drug bioavailability, reduce the dose and frequency of administration, and solve the problem of non-adherence to the prescribed therapy. This study systematically reviewed the recent advances in PLGA micro/nanoparticle delivery systems as a novel therapeutic approach for drug-resistant tuberculosis.

Inhalable dry powders of rifampicin highlighting potential and drawbacks in formulation development for experimental tuberculosis aerosol therapy.

Introduction: Recently, tuberculosis was reported as the leading cause of death from a single infectious agent. Standard therapy includes administration of four first-line antibiotics, i.e. rifampicin, isoniazid, ethambutol, and pyrazinamide over a period of at least 26 weeks, which in case of rifampicin oftentimes is accompanied by unwanted side effects and variable bioavailability that compromise a positive therapeutic outcome. As the main site of infection is the lungs, it is desirable to develop a therapeutic formulation to be administered via the pulmonary route.Areas covered: This work presents a literature review on studies investigating inhalable dry powder formulations including rifampicin in the context of an experimental tuberculosis therapy, with a special focus on aerosol performance.Expert opinion: It was found that formulation approaches involving different strategies and functional excipients are under investigation but as of now, no formulation has managed to leap into commercial clinical testing. Reasons for this might not primarily be associated with a lack of suitable candidates, but amongst others a lack of suitable in vitro models to assess the efficacy, therapeutic benefit, and cost-effectiveness of the candidate formulations.

Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular drugs.

Pulmonary tuberculosis accounts for 80% of cases and the delivery of antitubercular drugs into the lungs allows targeting the infected organ and, possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as matrix of inhalable microparticles that associate two first-line antitubercular drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed of fucose and sulphated sugar residues, moieties described as being recognised by surface receptors of alveolar macrophages, which host mycobacteria. Inhalable fucoidan microparticles loaded with antitubercular drugs were successfully produced with high association efficiencies of either isoniazid (95%) or rifabutin (81%). The microparticles evidenced no cytotoxicity on lung epithelial cells (A549). However, rifabutin-loaded microparticles showed a certain degree of toxicity on macrophage-like cells (THP-1) at the highest tested concentration (1 mg/mL). Furthermore, microparticles showed favourable aerodynamic properties for deep lung delivery (MMAD 2.0-3.8 µm) and, thus, show potential for an application as inhalable tuberculosis therapy.

Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles.

Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 µm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy.