A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilmassociated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance

Study on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity

Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury (ALI). Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations consist of nanoparticles (NPs) have several advantages over other administration routes therefore this study investigated the application of apigenin loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction. The influence of dispersibility enhancers(lactose monohydrate and L-leucine) on the in vitro aerosol deposition using a next generation impactor (NGI) was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using Franz cell apparatus. The antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH˙) free radical scavenging assay. Results: The encapsulation efficiency and the drug loading was measured to be 82.61 ± 4.56% and 7.51 ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray dried BSA-Api-NPs possessed good the aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose and fine particle fraction. The aerodynamic properties was enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH˙ assay confirmed that the antioxidant activity of encapsulated Api was preserved. Conclusion: This study provides evidence to support that albumin nanoparticles 49 are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs is a novel delivery system against lung injury with potential antioxidant activity

Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81 μg/capsule = 60 mg/kg MO), medium (15.97 μg/capsule = 90 mg/kg MO) and high (23.23 μg/capsule = 127 mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60 mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena