Functional lipids and lipoplexes for improved gene delivery

Zhang, Xiaoxiang; McIntosh, Thomas J.; Grinstaff, Mark W.

doi:10.1016/j.biochi.2011.05.005

Cited by 137 publications

(95 citation statements)

References 179 publications

(165 reference statements)

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“…Only a few studies have been published on the interaction of liposomes with prokaryotic cells. 32,33 Our result undoubtedly seems to correlate with these groups and, therefore, a possible mechanism to the fusion process between fluid liposomes and gram-negative bacteria was explained. Due to phosphatidylglycerol (PG) and LPS, liposomes have a negative charge.…”

supporting

confidence: 65%

“…[26][27][28][29][30] Liposomes have been successfully used in the delivery of bioactive proteins into flagellated E. coli envelope, 31 and to transfect competent E. coli and Mycoplasma capricolum cells with encapsulated plasmid DNA. 32,33 By using liposomes made of lipid extracts from the whole bacterial membranes of Salmonella minnesota RE595 (the composition and lipids were not identified), Tomlinson et al 33 successfully incorporated phospholipid and proteins into gram-negative bacteria and confirmed that a fusion process was involved in this extensive phospholipid transfer. In this paper, we reported liposome-bacteria fusion with: 1) an artificial liposome of known lipid composition; and 2) intact bacterial cells (both gram-positive and gram-negative).…”

Section: Discussionmentioning

confidence: 99%

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Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Wang¹,

Ma²,

Khalil³

et al. 2016

IJN

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Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. Methods In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipa lmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol) in a fluid state, and intact bacterial cells, by lipid mixing assay. Results The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66%) or P. aeruginosa (44%) seems to be correlated to their outer membrane phosphatidylethanolamine (PE) phospholipids composition (91% and 71%, respectively). Divalent cations increased the degree of fusion in the sequence Fe 2+ > Mg 2+ > Ca 2+ > Ba 2+ whereas temperatures lower than the phase transition temperature of DPPC/DMPG (9:1) vesicles decreased their fusion capacity. Acidic as well as basic pHs conferred higher degrees of fusion (54% and 45%, respectively) when compared to neutral pH (35%). Conclusion Based on the results of this study, a possible mechanism involving cationic bridging between bacterial negatively charged lipopolysaccharide and fluid liposomes DMPG phospholipids was outlined. Furthermore, the fluid liposomal-encapsulated tobramycin was prepared, and the in vitro bactericidal effects were also investigated.

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supporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Wang¹,

Ma²,

Khalil³

et al. 2016

IJN

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“…Many cationic lipids have been employed as synthetic carriers for gene therapy, but only a handful of these compounds have been investigated in clinical trials [13]. Cationic lipids are amphiphilic organic molecules, typically made up of three domains: a cationic head that allows binding to NA; a hydrophobic motif; and a linker separating these two elements [13].…”

Section: Use Of Cationic Lipids In Gene Delivery Systemsmentioning

confidence: 99%

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Belmadi

Midoux

Loyer

et al. 2015

Biotechnology Journal

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Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between efficacy and tolerance. The methods of administration and the vectors used are selected depending on whether the goal of treatment is the production of an active protein; the replacement of a missing or inactive gene; or the combat of acquired diseases, such as cancer or AIDS. In that sense, synthetic vectors represent a valuable solution because they are well characterized, their structure can be fine tuned, and their potential toxicity can be reduced, since toxicity depends on the composition of the formulations. Here we review various synthetic vectors for gene delivery and address the question of their biodistribution as a function of the route of administration. We highlight the modifications to vectors structure and formulations necessary to overcome the major hurdles limiting the effectiveness of nucleic acid therapies.

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“…However, DNA requires delivery to the nucleus for transcription. Movement of macromolecules through the cytoplasm is greatly restricted due to overcrowding of organelles, the cytoskeleton of the cell and high protein concentrations which slows mobility of the vector and exposes it to the degradative action of endonucleases [91,92]. For successful transfection to occur, the gene delivery vector must protect the cargo and actively traffic the nucleic acid payload towards the nucleus.…”

Section: Nuclear Traffickingmentioning

confidence: 99%

Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

2016

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The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective non-viral delivery systems can be applied successfully in oncology.Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration.

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Functional lipids and lipoplexes for improved gene delivery

Cited by 137 publications

References 179 publications

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

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