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Influence of poly(e...
Influence of poly(ethylene glycol) grafting density and polymer length on liposomes : Relating plasma circulation lifetimes to protein binding
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Dos Santos, Nancy (författare)
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Allen, Christine (författare)
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Doppen, Anne-Marie (författare)
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Anantha, Malathi (författare)
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Cox, Kelly A K (författare)
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Gallagher, Ryan C (författare)
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- Karlsson, Göran (författare)
- Uppsala universitet,Fysikalisk kemi
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- Edwards, Katarina (författare)
- Uppsala universitet,Fysikalisk kemi
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Kenner, Gail (författare)
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Samuels, Lacey (författare)
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Webb, Murray S (författare)
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Bally, Marcel B (författare)
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(creator_code:org_t)
- Elsevier BV, 2007
- 2007
- Engelska.
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1768:6, s. 1367-1377
- Relaterad länk:
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http://www.ncbi.nlm....
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The incorporation of poly(ethylene glycol) (PEG)-conjugated lipids in lipid-based carriers substantially prolongs the circulation lifetime of liposomes. However, the mechanism(s) by which PEG-lipids achieve this have not been fully elucidated. It is believed that PEG-lipids mediate steric stabilization, ultimately reducing surface-surface interactions including the aggregation of liposomes and/or adsorption of plasma proteins. The purpose of the studies described here was to compare the effects of PEG-lipid incorporation in liposomes on protein binding, liposome-liposome aggregation and pharmacokinetics in mice. Cholesterol-free liposomes were chosen because of their increasing importance as liposomal delivery systems and their marked sensitivity to protein binding and aggregation. Specifically, liposomes containing various molecular weight PEG-lipids at a variety of molar proportions were analyzed for in vivo clearance, aggregation state (size exclusion chromatography, quasi-elastic light scattering, cryo-transmission and freeze fracture electron microscopy) as well as in vitro and in vivo protein binding. The results indicated that as little as 0.5 mol% of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE) modified with PEG having a mean molecular weight of 2000 (DSPE-PEG(2000)) substantially increased plasma circulation longevity of liposomes prepared of 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC). Optimal plasma circulation lifetimes could be achieved with 2 mol% DSPE-PEG(2000). At this proportion of DSPE-PEG(2000), the aggregation of DSPC-based liposomes was completely precluded. However, the total protein adsorption and the protein profile was not influenced by the level of DSPE-PEG(2000) in the membrane. These studies suggest that PEG-lipids reduce the in vivo clearance of cholesterol-free liposomal formulations primarily by inhibition of surface interactions, particularly liposome-liposome aggregation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Cholesterol-free
- Liposomes
- PEG; Protein binding
- Plasma elimination
- MEDICINE
- MEDICIN
- PHARMACY
- FARMACI
- NATURAL SCIENCES
- NATURVETENSKAP
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Dos Santos, Nanc ...
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Allen, Christine
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Doppen, Anne-Mar ...
-
Anantha, Malathi
-
Cox, Kelly A K
-
Gallagher, Ryan ...
-
visa fler...
-
Karlsson, Göran
-
Edwards, Katarin ...
-
Kenner, Gail
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Samuels, Lacey
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Webb, Murray S
-
Bally, Marcel B
-
visa färre...
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Uppsala universitet