Liposomal drug delivery to manage nontuberculous mycobacterial pulmonary disease and other chronic lung infections

Abstract

Nontuberculous mycobacterial (NTM) pulmonary disease is a chronic respiratory infection associated with declining lung function, radiological deterioration and significantly increased morbidity and mortality. Patients often have underlying lung conditions, particularly bronchiectasis and COPD. NTM pulmonary disease is difficult to treat because mycobacteria can evade host defences and antimicrobial therapy through extracellular persistence in biofilms and sequestration into macrophages. Management of NTM pulmonary disease remains challenging and outcomes are often poor, partly due to limited penetration of antibiotics into intracellular spaces and biofilms. Efficient drug delivery to the site of infection is therefore a key objective of treatment, but there is high variability in lung penetration by antibiotics. Inhalation is the most direct route of delivery and has demonstrated increased efficacy of antibiotics like amikacin compared with systemic administration. Liposomes are small, artificial, enclosed spherical vesicles, in which drug molecules can be encapsulated to provide controlled release, with potentially improved pharmacokinetics and reduced toxicity. They are especially useful for drugs where penetration of cell membranes is essential. Inhaled delivery of liposomal drug solutions can therefore facilitate direct access to macrophages in the lung where the infecting NTM may reside. A range of liposomal drugs are currently being evaluated in respiratory diseases.

Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis

“…S7A). Recent studies have indicated that liposomes are widely used as drug carriers owing to their safety and ability to transport agents to target sites [ 14 ]. The prepared liposomes showed a 88% entrapment efficiency for loading ZNF416 siRNA with a zeta potential of 34.65 mV and hydrodynamic diameter of 146 nm (Fig.…”

New Auranofin Analogs with Antibacterial Properties against Burkholderia Clinical Isolates

“…One possible route is the creation of an MS-40S/MS-40-loaded liposome, as has been shown with rifampicin in the treatment of pulmonary Mycobacterium abscessus infections [ 54 ]. Creating an aerosolized antimicrobial therapy would also allow us to achieve higher concentrations of the drug, and increase lung penetration, which is especially important for CF pulmonary infections [ 55 ].…”

Meeting the challenges of NTM-PD from the perspective of the organism and the disease process: innovations in drug development and delivery

“…NTM are ubiquitous in the environment, rendering avoidance impossible [ 53 ]. Typically, NTM infection arises from inhalation of contaminated environmental particles such as aerosols and dust or aspiration of contaminated substances [ 18 , 40 , 50 ]. In the environment, biofilms containing NTM can be found in water distribution systems, while examples of intracellular niches include amoeba in water [ 54 , 55 ].…”

“…Many factors contribute to the challenges of treating NTM-PD; these include characteristics of the non-tuberculous mycobacteria (NTM) species and its intrinsic resistance capabilities [ 16 , 17 ] as well as the ability of NTM to evade host defences through sequestration in biofilms and macrophages in the lung, making effective antibiotic penetration and treatment difficult [ 18 ]. In addition, symptoms of NTM-PD are non-specific and mirror those of underlying conditions, and diagnosis is often delayed for a number of years for some patients who have moderate-to-severe symptoms at the time of diagnosis [ 19 – 21 ].…”