Jibriil P Ibrahim, Neville J Butcher, Ashok Kothapalli, Christopher N Subasic, Joanne T Blanchfield, Andrew K Whittaker, Michael R Whittaker, Lisa M Kaminskas
{"title":"肺部内源性白蛋白运输途径的利用有可能适度增加吸入给药后肺间质进入和药物递送系统的吸收。","authors":"Jibriil P Ibrahim, Neville J Butcher, Ashok Kothapalli, Christopher N Subasic, Joanne T Blanchfield, Andrew K Whittaker, Michael R Whittaker, Lisa M Kaminskas","doi":"10.1080/17425247.2023.2244881","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin.</p><p><strong>Methods: </strong>The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration.</p><p><strong>Results: </strong>Membrane permeability coefficient values (P<sub>app</sub>) of HSA increased in the order alveolar epithelia<small airway epithelia<microvascular endothelium, where the permeability of HSA through small airway and microvascular endothelia were approximately 4- and 28-fold higher than alveolar epithelia, respectively. Only 6.5% of the delivered BSA aerosol dose was absorbed from the lungs of sheep over 5 days, although half of the absorbed dose was absorbed via the lung lymph.</p><p><strong>Conclusion: </strong>Drug delivery systems that bind endogenous albumin may show a modest increase in lung permeability and absorption after inhaled delivery compared to systems that do not efficiently bind albumin.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1145-1155"},"PeriodicalIF":5.0000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration.\",\"authors\":\"Jibriil P Ibrahim, Neville J Butcher, Ashok Kothapalli, Christopher N Subasic, Joanne T Blanchfield, Andrew K Whittaker, Michael R Whittaker, Lisa M Kaminskas\",\"doi\":\"10.1080/17425247.2023.2244881\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin.</p><p><strong>Methods: </strong>The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration.</p><p><strong>Results: </strong>Membrane permeability coefficient values (P<sub>app</sub>) of HSA increased in the order alveolar epithelia<small airway epithelia<microvascular endothelium, where the permeability of HSA through small airway and microvascular endothelia were approximately 4- and 28-fold higher than alveolar epithelia, respectively. Only 6.5% of the delivered BSA aerosol dose was absorbed from the lungs of sheep over 5 days, although half of the absorbed dose was absorbed via the lung lymph.</p><p><strong>Conclusion: </strong>Drug delivery systems that bind endogenous albumin may show a modest increase in lung permeability and absorption after inhaled delivery compared to systems that do not efficiently bind albumin.</p>\",\"PeriodicalId\":12229,\"journal\":{\"name\":\"Expert Opinion on Drug Delivery\",\"volume\":\" \",\"pages\":\"1145-1155\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2244881\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2244881","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration.
Objectives: Drug delivery systems typically show limited access to the lung interstitium and absorption after pulmonary delivery. The aim of this work was to undertake a proof-of-concept investigation into the potential of employing endogenous albumin and albumin absorption mechanisms in the lungs to improve lung interstitial access and absorption of inhaled drug delivery systems that bind albumin.
Methods: The permeability of human albumin (HSA) through monolayers of primary human alveolar epithelia, small airway epithelia, and microvascular endothelium were investigated. The pulmonary pharmacokinetics of bovine serum albumin (BSA) was also investigated in efferent caudal mediastinal lymph duct-cannulated sheep after inhaled aerosol administration.
Results: Membrane permeability coefficient values (Papp) of HSA increased in the order alveolar epithelia
Conclusion: Drug delivery systems that bind endogenous albumin may show a modest increase in lung permeability and absorption after inhaled delivery compared to systems that do not efficiently bind albumin.
期刊介绍：
Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
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