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<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.
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
|---|---|
| Enthalten in: |
Expert opinion on drug delivery - 20(2023), 8 vom: 03. Juli, Seite 1145-1155 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ibrahim, Jibriil P [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Aerosols |
|---|
| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 02.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/17425247.2023.2244881 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360351751 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360351751 | ||
| 003 | DE-627 | ||
| 005 | 20231226082831.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/17425247.2023.2244881 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1201.xml |
| 035 | |a (DE-627)NLM360351751 | ||
| 035 | |a (NLM)37535434 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ibrahim, Jibriil P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.11.2023 | ||
| 500 | |a Date Revised 02.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: Membrane permeability coefficient values (Papp) 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Albumin | |
| 650 | 4 | |a inhaled | |
| 650 | 4 | |a lung permeability | |
| 650 | 4 | |a nebulized | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a sheep | |
| 650 | 7 | |a Albumins |2 NLM | |
| 650 | 7 | |a Aerosols |2 NLM | |
| 700 | 1 | |a Butcher, Neville J |e verfasserin |4 aut | |
| 700 | 1 | |a Kothapalli, Ashok |e verfasserin |4 aut | |
| 700 | 1 | |a Subasic, Christopher N |e verfasserin |4 aut | |
| 700 | 1 | |a Blanchfield, Joanne T |e verfasserin |4 aut | |
| 700 | 1 | |a Whittaker, Andrew K |e verfasserin |4 aut | |
| 700 | 1 | |a Whittaker, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Kaminskas, Lisa M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Expert opinion on drug delivery |d 2004 |g 20(2023), 8 vom: 03. Juli, Seite 1145-1155 |w (DE-627)NLM159019028 |x 1744-7593 |7 nnns |
| 773 | 1 | 8 | |g volume:20 |g year:2023 |g number:8 |g day:03 |g month:07 |g pages:1145-1155 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/17425247.2023.2244881 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 20 |j 2023 |e 8 |b 03 |c 07 |h 1145-1155 | ||