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Full-Text Articles in Dentistry
On The Formulation Of Ph-Sensitive Liposomes With Long Circulation Times, Sérgio Simões, João Nuno Moreira, Cristina Fonseca, Nejat Düzgüneş, Maria C. Pedroso De Lima
On The Formulation Of Ph-Sensitive Liposomes With Long Circulation Times, Sérgio Simões, João Nuno Moreira, Cristina Fonseca, Nejat Düzgüneş, Maria C. Pedroso De Lima
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Strategies used to enhance liposome-mediated drug delivery in vivo include the enhancement of stability and circulation time in the bloodstream, targeting to specific tissues or cells, and facilitation of intracytoplasmic delivery. pH-sensitive liposomes have been developed to mediate the introduction of highly hydrophilic molecules or macromolecules into the cytoplasm. These liposomes destabilize under acidic conditions found in the endocytotic pathway, and usually contain phosphatidylethanolamine (PE) and titratable stabilizing amphiphiles. Formulations without PE have also been developed. Encapsulated compounds are thought to be transported into the cytoplasm through destabilization of or fusion with the endosome membrane. Incorporation of a low mole …
Efficient Gene Transfer By Transferrin Lipoplexes In The Presence Of Serum, Conchita Tros De Ilarduya, Nejat Düzgüneş
Efficient Gene Transfer By Transferrin Lipoplexes In The Presence Of Serum, Conchita Tros De Ilarduya, Nejat Düzgüneş
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Cationic lipids are being used increasingly as reagents for gene delivery both in vitro and in vivo. One of the limitations to the application of cationic lipid-DNA complexes (lipoplexes) in vivo is the inhibition of gene delivery by serum. In this study, we have shown that transferrin (Tf)-lipoplexes, which had transferrin adsorbed at their surface via electrostatic interactions, are much more effective than plain lipoplexes in transfecting cells in the presence of relatively high concentrations (up to 60%) of fetal bovine serum (FBS). Serum even enhanced transfection by Tf-lipoplexes composed of 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP)/dioleoylphosphatidylethanolamine (DOPE)/pCMVLacZ at high lipid/DNA (+/-) charge …
Human Serum Albumin Enhances Dna Transfection By Lipoplexes And Confers Resistance To Inhibition By Serum, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Human Serum Albumin Enhances Dna Transfection By Lipoplexes And Confers Resistance To Inhibition By Serum, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
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Cationic liposome-DNA complexes ('lipoplexes') are used as gene delivery vehicles and may overcome some of the limitations of viral vectors for gene therapy applications. The interaction of highly positively charged lipoplexes with biological macromolecules in blood and tissues is one of the drawbacks of this system. We examined whether coating cationic liposomes with human serum albumin (HSA) could generate complexes that maintained transfection activity. The association of HSA with liposomes composed of 1,2-dioleoyl-3-(trimethylammonium) propane and dioleoylphosphatidylethanolamine, and subsequent complexation with the plasmid pCMVluc greatly increased luciferase expression in epithelial and lymphocytic cell lines above that obtained with plain lipoplexes. The …
Mechanisms Of Gene Transfer Mediated By Lipoplexes Associated With Targeting Ligands Or Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Mechanisms Of Gene Transfer Mediated By Lipoplexes Associated With Targeting Ligands Or Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Pedro Pires, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
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Association of a targeting ligand such as transferrin, or an endosome disrupting peptide such as GALA, with cationic liposome-DNA complexes ('lipoplexes') results in a significant enhancement of transfection of several cell types. Although these strategies can overcome some of the barriers to gene delivery by lipoplexes, the mechanisms by which they actually enhance transfection is not known. In studies designed to establish the targeting specificity of transferrin, we found that apo-transferrin enhances transfection to the same extent as transferrin, indicating that internalization of the lipoplexes is mostly independent of transferrin receptors. These observations were reinforced by results obtained from competitive …
Transfection Of Human Macrophages By Lipoplexes Via The Combined Use Of Transferrin And Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Elizabeth Pretzer, Paul Dazin, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Transfection Of Human Macrophages By Lipoplexes Via The Combined Use Of Transferrin And Ph-Sensitive Peptides, Sérgio Simões, Vladimir Slepushkin, Elizabeth Pretzer, Paul Dazin, Rogério Gaspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
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The crucial function of macrophages in a variety of biological processes and pathologies render these cells important targets for gene therapeutic interventions. Commonly used synthetic gene delivery vectors have not been successful in transfecting these non-dividing cells. A combination strategy involving cationic liposomes to condense and carry DNA, transferrin to facilitate cellular uptake, and the pH-sensitive peptide GALA to promote endosome destabilization, resulted in significant expression of a luciferase gene. Transfection of macrophages was dependent on the degree of differentiation of the cells. The quaternary complexes of cationic liposomes, DNA, transferrin, and GALA exhibited a net negative charge, which may …
Gene Delivery By Negatively Charged Ternary Complexes Of Dna, Cationic Liposomes And Transferrin Or Fusigenic Peptides, Sérgio Simões, Vladimir Slepushkin, R. Caspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
Gene Delivery By Negatively Charged Ternary Complexes Of Dna, Cationic Liposomes And Transferrin Or Fusigenic Peptides, Sérgio Simões, Vladimir Slepushkin, R. Caspar, Maria C. Pedroso De Lima, Nejat Düzgüneş
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Potential problems with the use of viral vectors for gene therapy necessitate the development of efficient nonviral vectors. The association of transferrin, or the pH-sensitive peptide GALA, with cationic liposomes composed of 1,2-dioleoyl-3-(trimethylammonium) propane and its equimolar mixture with dioleoylphosphatidylethanolamine, under conditions where the liposome/DNA complex is negatively charged, drastically increased luciferase expression from pCMVluc. The percentage of cells transfected, measured by β-galactosidase expression, was also increased by about 10-fold. The zeta potential of the ternary complexes was lower than that of the liposome/DNA complexes. Transfection activity of positively charged complexes was also enhanced by association with transferrin, GALA or …