TY  - JOUR
U1  - Wissenschaftlicher Artikel
A1  - Huck, Benedikt C.
A1  - Thiyagarajan, Durairaj
A1  - Bali, Aghiad
A1  - Boese, Annette
A1  - Besecke, Karen F. W.
A1  - Hozsa, Constantin
A1  - Gieseler, Robert K.
A1  - Furch, Marcus
A1  - Carvalho-Wodarz, Cristiane
A1  - Waldow, Franziska
A1  - Schwudke, Dominik
A1  - Metelkina, Olga
A1  - Titz, Alexander
A1  - Huwer, Hanno
A1  - Schwarzkopf, Konrad
A1  - Hoppstädter, Jessica
A1  - Kiemer, Alexandra K.
A1  - Koch, Marcus
A1  - Loretz, Brigitta
A1  - Lehr, Claus-Michael
T1  - 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
JF  - Advanced healthcare materials
N2  - 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.
KW  - air-liquid interface
KW  - bedaquiline
KW  - liposomal dry powders
KW  - particle tracking
KW  - pulmonary surfactants
Y1  - 2022
UN  - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-713
U6  - https://doi.org/10.1002/adhm.202102117
DO  - https://doi.org/10.1002/adhm.202102117
VL  - 11
IS  - 11
SP  - 2102117
ER  -