Sulfhydryl Based Cationic Surfactants and the Impact of Polyanions on Disulfide Bond Formation: Implications for Gene Transfer Vectors

Fuchs, Scott; Buethe, David D.; Khanna, Anupama; Yadava, Preeti; Hughes, Jeffrey A.

doi:10.1080/10611860400000649

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…Several groups have developed lipid-based carrier systems that employ triggering mechanisms activated by pH − , disulfide exchange − , enzymes − , heat − , and photochemical reactions , for deploying the encapsulated contents in a site- and/or time-specific manner. The presence of low pH environments within ischemic tissues and endosomal compartments during receptor-mediated endocytosis and vesicle trafficking (Figure ) suggests that acid-triggering approaches should be a widely applicable activation strategy, since they would not require an external stimulus to initiate liposomal content release.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

et al. 2008

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An acid-cleavable PEG lipid, 1′-(4′-cholesteryloxy-3′-butenyl)-ω-methoxy-polyethylene [112] glycolate (CVEP), has been developed that produces stable liposomes when dispersed as a minor component (0.5-5 mol%) in 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Cleavage of CVEP at mildly acidic pH's results in dePEGylation of the latently fusogenic DOPE liposomes, thereby triggering the onset of contents release. This paper describes the synthesis of CVEP via a six step sequence starting from the readily available precursors 1,4-butanediol, cholesterol, and mPEG acid. The hydrolysis rates and release kinetics from CVEP:DOPE liposome dispersions as a function of CVEP loading, as well as the cryogenic transmission electron microscopy and pH-dependent monolayer properties of 9:91 CVEP:DOPE mixtures, also are reported. When folate-receptor positive KB cells were exposed to calcein-loaded 5:95 CVEP:DOPE liposomes containing 0.1 mol% folatemodified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene[76] glycolamide (folate-PEG-DSPE), efficient delivery of the calcein cargo to the cytoplasm of the cells was observed as determined by fluorescence microscopy and flow cytometry. Fluorescence resonance energy transfer analysis of lipid mixing in these cells was consistent with membrane-membrane fusion between the liposome and endosomal membranes.

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Section: Introductionmentioning

confidence: 99%

Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

et al. 2008

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“…The chemical delivery vectors-liposomes and polymers are both reported to be effective siRNA delivery agents. Previous evaluation of polyplexes and lipoplexes has demonstrated that due to their release characteristics, favoring unloading in the cytoplasm; liposomes may exhibit certain advantages as siRNA delivery agents over polymers (6). siTox siRNA when successfully transfected into the cells leads to apoptosis and cell death within 24-48 h and the degree of cell death can be correlated to siRNA delivery (http://www.dharmacon.com/ docs/siCONTROL%20Flier.pdf.…”

Section: Introductionmentioning

confidence: 99%

Effect of Lyophilization and Freeze-thawing on the Stability of siRNA-liposome Complexes

et al. 2007

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Abstract. The purpose of this research was to describe the application of lyophilization in the delivery of siRNA using cationic lipids by addressing the long-term formulation/stability issues associated with cationic lipids and to understand the mechanism of lyoprotection. siRNA liposomes complexes were formed in different potential cyro/lyoprotectants and subjected to either lyophilization or freeze thaw cycles. siRNA, liposomes and/or lipoplexes were tested for activity, SYBR Green I binding, cellular uptake and particle size. The lipoplexes when lyophilized in the presence of sugars as lyoprotectants could be lyophilized and reconstituted without loss of transfection efficacy but in ionic solutions they lost 65-75% of their functionality. The mechanism of this loss of activity was further investigated. The lyophilization process did not alter siRNA's intrinsic biological activity as was evident by the ability of lyophilized siRNA to retain functionality and SYBR green I binding ability. While the lipoplex size dramatically increased (∼50-70 times) after lyophilization in the absence of non-ionic lyoprotectants. This increase in size correlated to the decrease in cellular accumulation of siRNA and a decrease in activity. In conclusion, siRNAs can be applied in cationic lipid lyophilized formulations and these complexes represent a potential method of increasing the stability of pre-formed complex.

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“…These cationic amphiphiles are able to respond to a stimulus that changes their chemical or physical properties, facilitating DNA delivery. Synthetic vectors have been prepared that are responsive to pH, − reducing conditions, − enzymes, ,− or temperature. , Many of these functional vectors that degrade or change conformation were designed based on the specific steps in the transfection pathway. This pathway starts with cellular entry of the DNA−amphiphile complex by endocytosis, followed by endosomal escape, and finally nuclear targeting and DNA expression.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and In Vitro Transfection Activity of Charge-Reversal Amphiphiles for DNA Delivery

Zhang

Prata

Berlin³

et al. 2011

Bioconjugate Chem.

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A series of charge-reversal lipids were synthesized that possess varying chain lengths and end functionalities. These lipids were designed to bind and then release DNA based on a change in electrostatic interaction with DNA. Specifically, a cleavable ester linkage is located at the ends of the hydrocarbon chains. The DNA release from the amphiphile was tuned by altering the length and position of the ester linkage in the hydrophobic chains of the lipids through the preparation of five new amphiphiles. The amphiphiles and corresponding lipoplexes were characterized by DSC, TEM, and X-ray, as well as evaluated for DNA binding and DNA transfection. For one specific charge-reversal lipid, stable lipoplexes of approximately 550 nm were formed, and with this amphiphile, effective in vitro DNA transfection activities was observed.

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Sulfhydryl Based Cationic Surfactants and the Impact of Polyanions on Disulfide Bond Formation: Implications for Gene Transfer Vectors

Cited by 6 publications

References 19 publications

Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

Cytoplasmic Delivery of Liposomal Contents Mediated by an Acid-Labile Cholesterol-Vinyl Ether-PEG Conjugate

Effect of Lyophilization and Freeze-thawing on the Stability of siRNA-liposome Complexes

Synthesis, Characterization, and In Vitro Transfection Activity of Charge-Reversal Amphiphiles for DNA Delivery

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