New Sterically Stabilized Vesicles Based on Nonionic Surfactant, Cholesterol, and Poly(Ethylene Glycol)-Cholesterol Conjugates

Beugin, Sophie; Edwards, Katarina; Karlsson, Göran; Ollivon, Michel; Lesieur, Sylviane

doi:10.1016/s0006-3495(98)78026-9

Cited by 63 publications

(64 citation statements)

References 67 publications

(99 reference statements)

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“…Our pyrene fluorescence data suggest a lower aggregation limit of 100 nM for cholesteryl RNAs, which is 10-fold higher than the concentration at which unmodified cholesterol starts to aggregate (Renshaw et al 1983). In addition, the concentration at which micelles are fully formed is at least 10 mM, and thereby at least 10-fold higher than the value measured for cholesterol-oligoethylene glycol conjugates (Beugin et al 1998). This difference is probably caused by the attachment of RNA to the cholesterol, which should entropically disfavor micelle formation.…”

Section: Discussionmentioning

confidence: 66%

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Müller

Bartel²

2008

RNA

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During an early step in the evolution of life, RNA served both as genome and as catalyst, according to the RNA world hypothesis. For self-replication, the RNA organisms must have contained an RNA that catalyzes RNA polymerization. As a first step toward recapitulating an RNA world in the laboratory, a polymerase ribozyme was generated previously by in vitro evolution and design. However, the efficiency of this ribozyme is about 100-fold too low for self-replication because of a low affinity of the ribozyme to its primer/template substrate. To improve the substrate interactions by colocalizing ribozyme and substrate on micelles, we attached hydrophobic anchors to both RNAs. We show here that the hydrophobic anchors led to aggregates with the expected size of the corresponding micelles. The micelle formation increased the polymerization yield of full-length products by 3-to 20-fold, depending on substrates and reaction conditions. With the best-characterized substrate, the improvement in polymerization efficiency was primarily due to reduced sequence-specific stalling on partially extended substrates. We discuss how, during the origin of life, micellar ribozyme aggregates could have acted as precursors to membraneencapsulated life forms.

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Section: Discussionmentioning

confidence: 66%

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Müller

Bartel²

2008

RNA

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“…28) Niosomes prepared by C16G2/cholesterol/M-polyethylene glycol (PEG)-Chol show spherical vesicles with diameters ranging from 20 to 200 nm. 22,29) 5.2. Temperature of Hydration Shape and size of niosome is also influenced by the hydration temperature.…”

Section: Membrane Additivesmentioning

confidence: 99%

Niosomes: A Controlled and Novel Drug Delivery System

Rajera

Nagpal

Singh

et al. 2011

Biological & Pharmaceutical Bulletin

293

162

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During the past decade formulation of vesicles as a tool to improve drug delivery, has created a lot of interest amongst the scientist working in the area of drug delivery systems. Vesicular system such as liposomes, niosomes, transferosomes, pharmacosomes and ethosomes provide an alternative to improve the drug delivery. Niosomes play an important role owing to their nonionic properties, in such drug delivery system. Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it should deliver the drug in accordance with a predetermined rate and second it should release therapeutically effective amount of drug at the site of action. Conventional dosage forms are unable to meet these requisites. Niosomes are essentially non-ionic surfactant based multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed by a membrane resulting from the organization of surfactant macromolecules as bilayer. Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates imbibing or encapsulating the hydrating aqueous solution. The main aim of development of niosomes is to control the release of drug in a sustained way, modification of distribution profile of drug and for targeting the drug to the specific body site. This paper deals with composition, characterization/evaluation, merits, demerits and applications of niosomes.

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“…The lack of a better protection by using a longer polymer, compared with the same mol% of PEG 2000 , may be explained by the high flexibility of the polymer, allowing antibodies to be "trapped" in the densely packed layer of PEG in the brush conformation, thus affecting the off-rate of the antibody. In addition, the actual amount of PEG-lipids incorporated may not be as high as 10 mol% because the maximum allowable PEG-lipid contents in liposome tend to decrease with increasing polymer size (Beugin et al, 1998). Another confounding factor not considered in these studies is the influence of enhanced nonspecific protein binding to PEGylated liposomes (Johnstone et al, 2001), an effect that will be particularly relevant for in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Antibody-Mediated Elimination of Ligand-Targeted Liposomes by Using Poly(Ethylene glycol)-Modified Lipids

Li¹,

Mayer²,

Bally³

2002

J Pharmacol Exp Ther

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One of the major obstacles in the development of ligandtargeted liposomes is poor liposome circulation longevity as a result of antibody-mediated elimination of these highly immunogenic carriers. Because studies from our laboratory suggest that it is not possible to reduce the immunogenicity of ligandconjugated liposomes by using surface-grafted poly(ethylene glycol) (PEG), we investigated the usefulness of PEG in protecting hapten-conjugated liposomes from elimination by an existing immune response that was previously established against the hapten. Using biotin as a model hapten, a strong biotinspecific antibody response was generated in mice by using bovine serum albumin-biotin. When these animals were challenged with liposomes containing biotin-conjugated lipid (1 or 0.1%), these liposomes were rapidly eliminated. Incorporation of PEG-lipids into these liposomes substantially reduced biotinspecific antibody binding as measured using an in vitro antibody consumption assay. However, depending on the hapten concentration, significant reductions in antibody binding through the use of PEG-lipids may not be sufficient to protect these liposomes from rapid elimination in vivo. Complete protection of liposomes was only achieved when the biotin concentration on liposome surface was low (0.1%) and with 5 mol% of either 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] or 1,2-dipalmatoyl-sn-glycero-3-phosphoethanolamine-n-methoxy(polyethylene glycol)-2000]. The use of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] (up to 15 mol%) was not effective in protecting liposomes from rapid elimination in vivo, indicating the limited usefulness of this highly exchangeable PEG-lipid. In conclusion, our in vivo and in vitro data indicate that liposomes can be protected from antibody-mediated elimination by using the right type and concentration of PEG-lipids. This result has important implication in the development of ligand-targeted liposomes.Active targeting can be achieved by conjugating macromolecules such as antibodies, peptides, and ligands of natural receptors onto liposome surfaces to improve the specificity of these drug carriers to disease sites (Vingerhoeds et al., 1994). Although active targeting of liposomes has met with some success both in vitro and in vivo (Park et al., 1995;Kirpotin et al., 1997;Gabizon et al., 1999), further development of ligand-targeted liposomes for in vivo use remains a challenge due to the immunogenicity of the drug carriers bearing surface ligands that function as antigenic haptens (Phillips and Emili, 1991;Phillips et al., 1994;Phillips and Dahman, 1995). Repeated administration of these liposomes becomes problematic because the pharmacokinetic and biodistribution behaviors of the carrier change after subsequent injections of the drug carrier (Shek and Heath, 1983;Phillips and Emili, 1991;Phillips et al., 1994;Harding et al., 1997;Tardi et al., 1997;Dams et al., 2000). Enhanced elimination of the liposomes...

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New Sterically Stabilized Vesicles Based on Nonionic Surfactant, Cholesterol, and Poly(Ethylene Glycol)-Cholesterol Conjugates

Cited by 63 publications

References 67 publications

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Improved polymerase ribozyme efficiency on hydrophobic assemblies

Niosomes: A Controlled and Novel Drug Delivery System

Prevention of Antibody-Mediated Elimination of Ligand-Targeted Liposomes by Using Poly(Ethylene glycol)-Modified Lipids

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