Photoinduced release of contents from sterically stabilized liposomes

Persistent Link:
http://hdl.handle.net/10150/284207
Title:
Photoinduced release of contents from sterically stabilized liposomes
Author:
Bondurant, Bruce
Issue Date:
2000
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The design of sterically stabilized liposomes with surface grafted poly(ethylene glycol) (PEG-liposomes) for drug delivery requires a very low rate of leakage so that drugs will remain encapsulated during the 24 to 48 hr that these liposomes remain in circulation. This design can interfere with the rapid release of the encapsulated drugs at the site of action. An effective technique for the photodestabilization of PEG-liposomes is described. Photosensitive PEG-liposomes containing the polymerizable lipid 1,2-bis[10-(2',4 '-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (bis-SorbPC₁₇,₁₇) were prepared in the presence of a water soluble fluorescent probe and were polymerized with UV light (254 nm). Liposomes composed of PEG-DOPE/bis-SorbPC₁₇,₁₇/cholesterol/DOPC (15/30/40/15) showed a 200-fold increase in the rate of leakage at very high conversion of monomer (>98%). Liposomes composed of PEG-DSPE/bis-SorbPC₁₇,₁₇/cholesterol/DSPC (5/30/35/30) showed increases in the rate of leakage that were: 90-fold at only 20% conversion of monomer, 9-fold at 80 to 90% conversion, and 150-fold at greater than 95% conversion. These liposomes also exhibited a 17-fold increase in the rate of leakage near the main phase transition temperature (T(M)) of bis-SorbPC₁₇,₁₇ (28.8°C). These observations suggest that the polymerization of phase-separated domains of bis-SorbPC₁₇,₁₇ causes defects in the membrane that result in increased permeability. While the leakage kinetics at high conversion followed a first order rate law, leakage at low conversion did not. This, as well as the biphasic dependence of the rate of release on irradiation time in liposomes exhibiting enhanced release at low conversion, indicate that the mechanisms of leakage at low and high conversion are different. Syntheses of neutral and polymerizable PEG-lipids as well as polymerizable phosphatidylcholines are described here. Neutral PEG-lipids were used to study the effect of lipid charge on mechanical properties of PEG-lipids and on the interactions of PEG-liposomes with cells. The compressibility of a neutral PEG grafted supported bilayer could be fitted most closely with the MWC mean field model for a polymer brush (Efremova et al. Biochemistry 2000 39: 3441--3451). Neutral liposomes were endocytosed at a significantly higher rate than anionic liposomes by HeLa ovarian carcinoma cells, while murine macrophage cells showed no preference (Miller et al. Biochemistry 1998 37: 12875--12883).
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Chemistry, Biochemistry.; Chemistry, Organic.; Chemistry, Polymer.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
O'Brien, David F.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titlePhotoinduced release of contents from sterically stabilized liposomesen_US
dc.creatorBondurant, Bruceen_US
dc.contributor.authorBondurant, Bruceen_US
dc.date.issued2000en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe design of sterically stabilized liposomes with surface grafted poly(ethylene glycol) (PEG-liposomes) for drug delivery requires a very low rate of leakage so that drugs will remain encapsulated during the 24 to 48 hr that these liposomes remain in circulation. This design can interfere with the rapid release of the encapsulated drugs at the site of action. An effective technique for the photodestabilization of PEG-liposomes is described. Photosensitive PEG-liposomes containing the polymerizable lipid 1,2-bis[10-(2',4 '-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphatidylcholine (bis-SorbPC₁₇,₁₇) were prepared in the presence of a water soluble fluorescent probe and were polymerized with UV light (254 nm). Liposomes composed of PEG-DOPE/bis-SorbPC₁₇,₁₇/cholesterol/DOPC (15/30/40/15) showed a 200-fold increase in the rate of leakage at very high conversion of monomer (>98%). Liposomes composed of PEG-DSPE/bis-SorbPC₁₇,₁₇/cholesterol/DSPC (5/30/35/30) showed increases in the rate of leakage that were: 90-fold at only 20% conversion of monomer, 9-fold at 80 to 90% conversion, and 150-fold at greater than 95% conversion. These liposomes also exhibited a 17-fold increase in the rate of leakage near the main phase transition temperature (T(M)) of bis-SorbPC₁₇,₁₇ (28.8°C). These observations suggest that the polymerization of phase-separated domains of bis-SorbPC₁₇,₁₇ causes defects in the membrane that result in increased permeability. While the leakage kinetics at high conversion followed a first order rate law, leakage at low conversion did not. This, as well as the biphasic dependence of the rate of release on irradiation time in liposomes exhibiting enhanced release at low conversion, indicate that the mechanisms of leakage at low and high conversion are different. Syntheses of neutral and polymerizable PEG-lipids as well as polymerizable phosphatidylcholines are described here. Neutral PEG-lipids were used to study the effect of lipid charge on mechanical properties of PEG-lipids and on the interactions of PEG-liposomes with cells. The compressibility of a neutral PEG grafted supported bilayer could be fitted most closely with the MWC mean field model for a polymer brush (Efremova et al. Biochemistry 2000 39: 3441--3451). Neutral liposomes were endocytosed at a significantly higher rate than anionic liposomes by HeLa ovarian carcinoma cells, while murine macrophage cells showed no preference (Miller et al. Biochemistry 1998 37: 12875--12883).en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectChemistry, Biochemistry.en_US
dc.subjectChemistry, Organic.en_US
dc.subjectChemistry, Polymer.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorO'Brien, David F.en_US
dc.identifier.proquest9983890en_US
dc.identifier.bibrecord.b40825310en_US
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