Lipidated brush-PEG polymers as low molecular weight pulmonary drug delivery platforms
OBJECTIVES: Nanomedicines are being actively developed as inhalable drug delivery systems. However, there is a distinct utility in developing smaller polymeric systems that can bind albumin in the lungs. We therefore examined the pulmonary pharmacokinetic behavior of a series of lipidated brush-PEG (5 kDa) polymers conjugated to 1C2, 1C12 lipid or 2C12 lipids.
METHODS: The pulmonary pharmacokinetics, patterns of lung clearance and safety of polymers were examined in rats. Permeability through monolayers of primary human alveolar epithelia, small airway epithelia and lung microvascular endothelium were also investigated, along with lung mucus penetration and cell uptake.
RESULTS: Polymers showed similar pulmonary pharmacokinetic behavior and patterns of lung clearance, irrespective of lipid molecular weight and albumin binding capacity, with up to 30% of the dose absorbed from the lungs over 24 h. 1C12-PEG showed the greatest safety in the lungs. Based on its larger size, 2C12-PEG also showed the lowest mucus and cell membrane permeability of the three polymers. While albumin had no significant effect on membrane transport, the cell uptake of C12-conjugated PEGs were increased in alveolar epithelial cells.
CONCLUSION: Lipidated brush-PEG polymers composed of 1C12 lipid may provide a useful and novel alternative to large nanomaterials as inhalable drug delivery systems.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Expert opinion on drug delivery - 21(2024), 1 vom: 28. Jan., Seite 151-167 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kaminskas, Lisa M [VerfasserIn] |
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| Links: |
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| Themen: |
3WJQ0SDW1A |
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| Anmerkungen: |
Date Completed 02.02.2024 Date Revised 02.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/17425247.2024.2305116 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367393662 |
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| 100 | 1 | |a Kaminskas, Lisa M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lipidated brush-PEG polymers as low molecular weight pulmonary drug delivery platforms |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: Nanomedicines are being actively developed as inhalable drug delivery systems. However, there is a distinct utility in developing smaller polymeric systems that can bind albumin in the lungs. We therefore examined the pulmonary pharmacokinetic behavior of a series of lipidated brush-PEG (5 kDa) polymers conjugated to 1C2, 1C12 lipid or 2C12 lipids | ||
| 520 | |a METHODS: The pulmonary pharmacokinetics, patterns of lung clearance and safety of polymers were examined in rats. Permeability through monolayers of primary human alveolar epithelia, small airway epithelia and lung microvascular endothelium were also investigated, along with lung mucus penetration and cell uptake | ||
| 520 | |a RESULTS: Polymers showed similar pulmonary pharmacokinetic behavior and patterns of lung clearance, irrespective of lipid molecular weight and albumin binding capacity, with up to 30% of the dose absorbed from the lungs over 24 h. 1C12-PEG showed the greatest safety in the lungs. Based on its larger size, 2C12-PEG also showed the lowest mucus and cell membrane permeability of the three polymers. While albumin had no significant effect on membrane transport, the cell uptake of C12-conjugated PEGs were increased in alveolar epithelial cells | ||
| 520 | |a CONCLUSION: Lipidated brush-PEG polymers composed of 1C12 lipid may provide a useful and novel alternative to large nanomaterials as inhalable drug delivery systems | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Poly(ethylene glycol) | |
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| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a polymeric drug delivery system | |
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| 700 | 1 | |a Butcher, Neville J |e verfasserin |4 aut | |
| 700 | 1 | |a Subasic, Christopher N |e verfasserin |4 aut | |
| 700 | 1 | |a Kothapalli, Ashok |e verfasserin |4 aut | |
| 700 | 1 | |a Haque, Shadabul |e verfasserin |4 aut | |
| 700 | 1 | |a Grace, James L |e verfasserin |4 aut | |
| 700 | 1 | |a Morsdorf, Alexander |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 Quinn, John F |e verfasserin |4 aut | |
| 700 | 1 | |a Whittaker, Michael R |e verfasserin |4 aut | |
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