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Nano-in-Microparticles for Aerosol Delivery of Antibiotic-Loaded, Fucose-Derivatized, and Macrophage-Targeted Liposomes to Combat Mycobacterial Infections: In Vitro Deposition, Pulmonary Barrier Interactions, and Targeted Delivery

  • Nontuberculous mycobacterial infections rapidly emerge and demand potent medications to cope with resistance. In this context, targeted loco-regional delivery of aerosol medicines to the lungs is an advantage. However, sufficient antibiotic delivery requires engineered aerosols for optimized deposition. Here, the effect of bedaquiline-encapsulating fucosylated versus nonfucosylated liposomes on cellular uptake and delivery is investigated. Notably, this comparison includes critical parameters for pulmonary delivery, i.e., aerosol deposition and the noncellular barriers of pulmonary surfactant (PS) and mucus. Targeting increases liposomal uptake into THP-1 cells as well as peripheral blood monocyte- and lung-tissue derived macrophages. Aerosol deposition in the presence of PS, however, masks the effect of active targeting. PS alters antibiotic release that depends on the drug's hydrophobicity, while mucus reduces the mobility of nontargeted more than fucosylated liposomes. Dry-powder microparticles of spray-dried bedaquiline-loaded liposomes display a high fine particle fraction of >70%, as well as preserved liposomal integrity and targeting function. The antibiotic effect is maintained when deposited as powder aerosol on cultured Mycobacterium abscessus. When treating M. abscessus infected THP-1 cells, the fucosylated variant enabled enhanced bacterial killing, thus opening up a clear perspective for the improved treatment of nontuberculous mycobacterial infections.

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Document Type:Article
Author:Benedikt C. HuckORCiD, Durairaj Thiyagarajan, Aghiad Bali, Annette BoeseORCiD, Karen F. W. Besecke, Constantin HozsaORCiD, Robert K. Gieseler, Marcus Furch, Cristiane Carvalho-WodarzORCiD, Franziska WaldowORCiD, Dominik Schwudke, Olga MetelkinaORCiD, Alexander TitzORCiD, Hanno Huwer, Konrad SchwarzkopfORCiD, Jessica HoppstädterORCiD, Alexandra K. KiemerORCiD, Marcus Koch, Brigitta LoretzORCiD, Claus-Michael LehrORCiD
Parent Title (English):Advanced healthcare materials
First Page:2102117
Year of first Publication:2022
Release Date:2022/08/03
Tag:air-liquid interface; bedaquiline; liposomal dry powders; particle tracking; pulmonary surfactants
Impact:11.092 (2021)
Funding Information:German Federal Ministry of Education and Research. Grant Number: 16GW0167/GWANTA20 European Research Council: ERC Starting Grant Sweetbullets. Grant Number: 716311
Research Departments:Physikalische Analytik
DDC classes:500 Naturwissenschaften und Mathematik / 570 Biowissenschaften, Biologie
Open Access:Open Access
Signature:INM 2022/029
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International