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Liposomal drug delivery to manage nontuberculous mycobacterial pulmonary disease and other chronic lung infections
被引:21
|作者:
Chalmers, James D.
[1
]
van Ingen, Jakko
[2
]
van der Laan, Roald
[3
]
Herrmann, Jean-Louis
[4
,5
]
机构:
[1] Univ Dundee, Ninewells Hosp & Med Sch, Scottish Ctr Resp Res, Dundee, Scotland
[2] Radboud Univ Nijmegen, Radboudumc Ctr Infect Dis, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands
[3] Insmed BV, Utrecht, Netherlands
[4] Univ Paris Saclay, UVSQ, Infect & Inflammat, INSERM, Montigny Le Bretonneux, France
[5] Grp Hosp Univ Paris Saclay, Hop Raymond Poincare, AP HP, Garches, France
来源:
关键词:
PSEUDOMONAS-AERUGINOSA INFECTION;
MECHANICALLY VENTILATED PATIENTS;
TIME-KILL KINETICS;
AVIUM COMPLEX;
CYSTIC-FIBROSIS;
CELL-WALL;
AMIKACIN CONCENTRATIONS;
ENCAPSULATED-AMIKACIN;
RESISTANCE MECHANISMS;
ABSCESSUS COMPLEX;
D O I:
10.1183/16000617.0010-2021
中图分类号:
R56 [呼吸系及胸部疾病];
学科分类号:
摘要:
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.
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