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 deposit...
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| Veröffentlicht in: | Advanced healthcare materials 2022-06, Vol.11 (11), p.e2102117-n/a |
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| creator | Huck, Benedikt C. Thiyagarajan, Durairaj Bali, Aghiad Boese, Annette Besecke, Karen F. W. Hozsa, Constantin Gieseler, Robert K. Furch, Marcus Carvalho‐Wodarz, Cristiane Waldow, Franziska Schwudke, Dominik Metelkina, Olga Titz, Alexander Huwer, Hanno Schwarzkopf, Konrad Hoppstädter, Jessica Kiemer, Alexandra K. Koch, Marcus Loretz, Brigitta Lehr, Claus‐Michael |
| description | 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.
Nano‐in‐microparticles for aerosol delivery of antibiotic‐loaded and fucose‐derivatized liposomes are developed to combat mycobacterial infections. In vitro studies with various phagocytic cell types reveal the benefits of macrophage‐targeted pulmonary delivery, which oftentimes is complicated by the interaction of antibiotics with pulmonary barriers, if delivered in nonencapsulated form. The inclusion of pulmonary mucus and surfactant into such models helps to estimate key factors that may influence therapeutic outcomes. |
| doi_str_mv | 10.1002/adhm.202102117 |
| format | Article |
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Nano‐in‐microparticles for aerosol delivery of antibiotic‐loaded and fucose‐derivatized liposomes are developed to combat mycobacterial infections. In vitro studies with various phagocytic cell types reveal the benefits of macrophage‐targeted pulmonary delivery, which oftentimes is complicated by the interaction of antibiotics with pulmonary barriers, if delivered in nonencapsulated form. The inclusion of pulmonary mucus and surfactant into such models helps to estimate key factors that may influence therapeutic outcomes.</description><identifier>ISSN: 2192-2640</identifier><identifier>ISSN: 2192-2659</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.202102117</identifier><identifier>PMID: 35112802</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Administration, Inhalation ; Aerosols ; air–liquid interfaces ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; bedaquiline ; Deposition ; Dry Powder Inhalers ; Fucose ; Hydrophobicity ; Infections ; liposomal dry powders ; Liposomes ; Lung ; Lungs ; Macrophages ; Microparticles ; Monocytes ; Mucus ; Particle Size ; particle tracking ; Peripheral blood ; Powders ; pulmonary surfactants</subject><ispartof>Advanced healthcare materials, 2022-06, Vol.11 (11), p.e2102117-n/a</ispartof><rights>2022 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH</rights><rights>2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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W.</creatorcontrib><creatorcontrib>Hozsa, Constantin</creatorcontrib><creatorcontrib>Gieseler, Robert K.</creatorcontrib><creatorcontrib>Furch, Marcus</creatorcontrib><creatorcontrib>Carvalho‐Wodarz, Cristiane</creatorcontrib><creatorcontrib>Waldow, Franziska</creatorcontrib><creatorcontrib>Schwudke, Dominik</creatorcontrib><creatorcontrib>Metelkina, Olga</creatorcontrib><creatorcontrib>Titz, Alexander</creatorcontrib><creatorcontrib>Huwer, Hanno</creatorcontrib><creatorcontrib>Schwarzkopf, Konrad</creatorcontrib><creatorcontrib>Hoppstädter, Jessica</creatorcontrib><creatorcontrib>Kiemer, Alexandra K.</creatorcontrib><creatorcontrib>Koch, Marcus</creatorcontrib><creatorcontrib>Loretz, Brigitta</creatorcontrib><creatorcontrib>Lehr, Claus‐Michael</creatorcontrib><title>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</title><title>Advanced healthcare materials</title><addtitle>Adv Healthc Mater</addtitle><description>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.
Nano‐in‐microparticles for aerosol delivery of antibiotic‐loaded and fucose‐derivatized liposomes are developed to combat mycobacterial infections. In vitro studies with various phagocytic cell types reveal the benefits of macrophage‐targeted pulmonary delivery, which oftentimes is complicated by the interaction of antibiotics with pulmonary barriers, if delivered in nonencapsulated form. 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W.</au><au>Hozsa, Constantin</au><au>Gieseler, Robert K.</au><au>Furch, Marcus</au><au>Carvalho‐Wodarz, Cristiane</au><au>Waldow, Franziska</au><au>Schwudke, Dominik</au><au>Metelkina, Olga</au><au>Titz, Alexander</au><au>Huwer, Hanno</au><au>Schwarzkopf, Konrad</au><au>Hoppstädter, Jessica</au><au>Kiemer, Alexandra K.</au><au>Koch, Marcus</au><au>Loretz, Brigitta</au><au>Lehr, Claus‐Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Advanced healthcare materials</jtitle><addtitle>Adv Healthc Mater</addtitle><date>2022-06-01</date><risdate>2022</risdate><volume>11</volume><issue>11</issue><spage>e2102117</spage><epage>n/a</epage><pages>e2102117-n/a</pages><issn>2192-2640</issn><issn>2192-2659</issn><eissn>2192-2659</eissn><abstract>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.
Nano‐in‐microparticles for aerosol delivery of antibiotic‐loaded and fucose‐derivatized liposomes are developed to combat mycobacterial infections. In vitro studies with various phagocytic cell types reveal the benefits of macrophage‐targeted pulmonary delivery, which oftentimes is complicated by the interaction of antibiotics with pulmonary barriers, if delivered in nonencapsulated form. The inclusion of pulmonary mucus and surfactant into such models helps to estimate key factors that may influence therapeutic outcomes.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35112802</pmid><doi>10.1002/adhm.202102117</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-5864-8462</orcidid><orcidid>https://orcid.org/0000-0003-0057-5181</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2192-2640 |
| ispartof | Advanced healthcare materials, 2022-06, Vol.11 (11), p.e2102117-n/a |
| issn | 2192-2640 2192-2659 2192-2659 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11468583 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Administration, Inhalation Aerosols air–liquid interfaces Anti-Bacterial Agents - pharmacology Antibiotics bedaquiline Deposition Dry Powder Inhalers Fucose Hydrophobicity Infections liposomal dry powders Liposomes Lung Lungs Macrophages Microparticles Monocytes Mucus Particle Size particle tracking Peripheral blood Powders pulmonary surfactants |
| title | 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T20%3A43%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Nano%E2%80%90in%E2%80%90Microparticles%20for%20Aerosol%20Delivery%20of%20Antibiotic%E2%80%90Loaded,%20Fucose%E2%80%90Derivatized,%20and%20Macrophage%E2%80%90Targeted%20Liposomes%20to%20Combat%20Mycobacterial%20Infections:%20In%20Vitro%20Deposition,%20Pulmonary%20Barrier%20Interactions,%20and%20Targeted%20Delivery&rft.jtitle=Advanced%20healthcare%20materials&rft.au=Huck,%20Benedikt%20C.&rft.date=2022-06-01&rft.volume=11&rft.issue=11&rft.spage=e2102117&rft.epage=n/a&rft.pages=e2102117-n/a&rft.issn=2192-2640&rft.eissn=2192-2659&rft_id=info:doi/10.1002/adhm.202102117&rft_dat=%3Cproquest_pubme%3E2625272357%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2673813236&rft_id=info:pmid/35112802&rfr_iscdi=true |