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Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics., Objectives: This study aimed to investigate whether nebulisation is suitable for delivering Lacticaseibacillus rhamnosus GG (LGG) into the lungs for the potential treatment of bacterial pulmonary infections., Methods: It compared the dose output and aerosol performance of a vibrating-mesh nebuliser (VMN) and a jet nebuliser (JN) in nebulising LGG suspended in de Man Rogosa Sharpe (MRS) broth, phosphate-buffered saline (PBS), or normal saline (0.9% w / v sodium chloride in water)., Results: The VMN consistently produced a higher output than the JN for all liquid media, indicating that VMN was more efficient. The fine-particle fractions of both nebulisers were comparable for a given medium. The highest fine-particle fraction was achieved with LGG suspended in MRS broth for both nebulisers (20.5 ± 2.8% for VMN; 18.7 ± 3.4% for JN). This suggests that the aerosol performance of nebulised probiotics may depend on the medium in which the probiotic bacteria were suspended., Conclusions: Therefore, this study demonstrated that the nebulisation efficiency of LGG depended on the nebuliser type and liquid medium of the probiotic suspension.

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin ( w / w ) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3-5.2 µm, with about 50-60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.