Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep
Enhancing the delivery of therapeutic agents to the lung lymph, including drugs, transfection agents, vaccine antigens and vectors, has the potential to significantly improve the treatment and prevention of a range of lung-related illnesses. One way in which lymphatic delivery can be optimized is vi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.880448/full |
| _version_ | 1811340726476210176 |
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| author | Jibriil P Ibrahim Shadabul Haque Robert J Bischof Andrew K Whittaker Michael R Whittaker Lisa M Kaminskas |
| author_facet | Jibriil P Ibrahim Shadabul Haque Robert J Bischof Andrew K Whittaker Michael R Whittaker Lisa M Kaminskas |
| author_sort | Jibriil P Ibrahim |
| collection | DOAJ |
| description | Enhancing the delivery of therapeutic agents to the lung lymph, including drugs, transfection agents, vaccine antigens and vectors, has the potential to significantly improve the treatment and prevention of a range of lung-related illnesses. One way in which lymphatic delivery can be optimized is via the use of nanomaterial-based carriers, such as liposomes. After inhaled delivery however, there is conflicting information in the literature regarding whether nanomaterials can sufficiently access the lung lymphatics to have a therapeutic benefit, in large part due to a lack of reliable quantitative pharmacokinetic data. The aim of this work was to quantitatively evaluate the pulmonary lymphatic pharmacokinetics of a model nanomaterial-based drug delivery system (HSPC liposomes) in caudal mediastinal lymph duct cannulated sheep after nebulized administration to the lungs. Liposomes were labelled with 3H-phosphatidylcholine to facilitate evaluation of pharmacokinetics and biodistribution in biological samples. While nanomaterials administered to the lungs may access the lymphatics via direct absorption from the airways or after initial uptake by alveolar macrophages, only 0.3 and 0.001% of the 3H-lipid dose was recovered in lung lymph fluid and lymph cell pellets (containing immune cells) respectively over 5 days. This suggests limited lymphatic access of liposomes, despite apparent pulmonary bioavailability of the 3H-lipid being approximately 17%, likely a result of absorption of liberated 3H-lipid after breakdown of the liposome in the presence of lung surfactant. Similarly, biodistribution of 3H in the mediastinal lymph node was insignificant after 5 days. These data suggest that liposomes, that are normally absorbed via the lymphatics after interstitial administration, do not access the lung lymphatics after inhaled administration. Alternate approaches to maximize the lung lymphatic delivery of drugs and other therapeutics need to be identified. |
| first_indexed | 2024-04-13T18:46:08Z |
| format | Article |
| id | doaj.art-518e5ad5e4ac4d40a7a4da69ec00a08c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T18:46:08Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-518e5ad5e4ac4d40a7a4da69ec00a08c2022-12-22T02:34:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.880448880448Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in SheepJibriil P Ibrahim0Shadabul Haque1Robert J Bischof2Andrew K Whittaker3Michael R Whittaker4Lisa M Kaminskas5School of Biomedical Sciences, University of Queensland, St Lucia, QLD, AustraliaMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, AustraliaSchool of Science, Psychology and Sport, Federation University, Berwick, VIC, AustraliaAustralian Institute for Bioengineering and Nanotechnology, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, AustraliaMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, AustraliaSchool of Biomedical Sciences, University of Queensland, St Lucia, QLD, AustraliaEnhancing the delivery of therapeutic agents to the lung lymph, including drugs, transfection agents, vaccine antigens and vectors, has the potential to significantly improve the treatment and prevention of a range of lung-related illnesses. One way in which lymphatic delivery can be optimized is via the use of nanomaterial-based carriers, such as liposomes. After inhaled delivery however, there is conflicting information in the literature regarding whether nanomaterials can sufficiently access the lung lymphatics to have a therapeutic benefit, in large part due to a lack of reliable quantitative pharmacokinetic data. The aim of this work was to quantitatively evaluate the pulmonary lymphatic pharmacokinetics of a model nanomaterial-based drug delivery system (HSPC liposomes) in caudal mediastinal lymph duct cannulated sheep after nebulized administration to the lungs. Liposomes were labelled with 3H-phosphatidylcholine to facilitate evaluation of pharmacokinetics and biodistribution in biological samples. While nanomaterials administered to the lungs may access the lymphatics via direct absorption from the airways or after initial uptake by alveolar macrophages, only 0.3 and 0.001% of the 3H-lipid dose was recovered in lung lymph fluid and lymph cell pellets (containing immune cells) respectively over 5 days. This suggests limited lymphatic access of liposomes, despite apparent pulmonary bioavailability of the 3H-lipid being approximately 17%, likely a result of absorption of liberated 3H-lipid after breakdown of the liposome in the presence of lung surfactant. Similarly, biodistribution of 3H in the mediastinal lymph node was insignificant after 5 days. These data suggest that liposomes, that are normally absorbed via the lymphatics after interstitial administration, do not access the lung lymphatics after inhaled administration. Alternate approaches to maximize the lung lymphatic delivery of drugs and other therapeutics need to be identified.https://www.frontiersin.org/articles/10.3389/fphar.2022.880448/fulllung lymphpharmacokineticssheepinhalationmediastinal lymphNanoparticles |
| spellingShingle | Jibriil P Ibrahim Shadabul Haque Robert J Bischof Andrew K Whittaker Michael R Whittaker Lisa M Kaminskas Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep Frontiers in Pharmacology lung lymph pharmacokinetics sheep inhalation mediastinal lymph Nanoparticles |
| title | Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep |
| title_full | Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep |
| title_fullStr | Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep |
| title_full_unstemmed | Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep |
| title_short | Liposomes are Poorly Absorbed via Lung Lymph After Inhaled Administration in Sheep |
| title_sort | liposomes are poorly absorbed via lung lymph after inhaled administration in sheep |
| topic | lung lymph pharmacokinetics sheep inhalation mediastinal lymph Nanoparticles |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.880448/full |
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