The Experts below are selected from a list of 13839 Experts worldwide ranked by ideXlab platform
Gabriele Candiani - One of the best experts on this subject based on the ideXlab platform.
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Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the Biological Environment
Journal of Nanoparticle Research, 2013Co-Authors: Daniele Pezzoli, Gabriele CandianiAbstract:Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.
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non viral gene delivery strategies for gene therapy a menage a trois among nucleic acids materials and the Biological Environment
Journal of Nanoparticle Research, 2013Co-Authors: Daniele Pezzoli, Gabriele CandianiAbstract:Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.
Daniele Pezzoli - One of the best experts on this subject based on the ideXlab platform.
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Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the Biological Environment
Journal of Nanoparticle Research, 2013Co-Authors: Daniele Pezzoli, Gabriele CandianiAbstract:Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.
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non viral gene delivery strategies for gene therapy a menage a trois among nucleic acids materials and the Biological Environment
Journal of Nanoparticle Research, 2013Co-Authors: Daniele Pezzoli, Gabriele CandianiAbstract:Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.
Chuanxian Ding - One of the best experts on this subject based on the ideXlab platform.
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improved stability of plasma sprayed dicalcium silicate zirconia composite coating
Thin Solid Films, 2006Co-Authors: Xuebin Zheng, Chuanxian DingAbstract:Dicalcium silicate/zirconia composite coatings were produced on Ti–6Al–4V substrates using atmospheric plasma spraying. Different weight ratios of zirconia (50 wt.%, 70 wt.%, 90 wt.%) were mechanically blended with dicalcium silicate (C2S) powders as feedstocks. The composite coatings were immersed in a simulated body fluid (SBF) and a Tris–HCl solution for the in vitro appraisement of stability and long-term performance in a Biological Environment. The ion concentration changes of Ca, Si, and P in SBF and Tris–HCl solution were monitored using inductively-coupled plasma atomic emission spectroscopy (ICP–AES). Compared to the pure C2S coating, our results show that the dissolution rate of the composite coatings is effectively reduced and the stability is improved by the addition of zirconia. The high content of zirconia in the coatings ensures the long-term performance in Biological Environment, while dissolution of C2S in the coatings results in a higher Ca ion concentration in SBF and rapid precipitation of bone-like apatite on the composite coating surfaces indicating good bioconductivity of the coatings.
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Improved stability of plasma-sprayed dicalcium silicate/zirconia composite coating
Thin Solid Films, 2006Co-Authors: Xuebin Zheng, Chuanxian DingAbstract:Dicalcium silicate/zirconia composite coatings were produced on Ti–6Al–4V substrates using atmospheric plasma spraying. Different weight ratios of zirconia (50 wt.%, 70 wt.%, 90 wt.%) were mechanically blended with dicalcium silicate (C2S) powders as feedstocks. The composite coatings were immersed in a simulated body fluid (SBF) and a Tris–HCl solution for the in vitro appraisement of stability and long-term performance in a Biological Environment. The ion concentration changes of Ca, Si, and P in SBF and Tris–HCl solution were monitored using inductively-coupled plasma atomic emission spectroscopy (ICP–AES). Compared to the pure C2S coating, our results show that the dissolution rate of the composite coatings is effectively reduced and the stability is improved by the addition of zirconia. The high content of zirconia in the coatings ensures the long-term performance in Biological Environment, while dissolution of C2S in the coatings results in a higher Ca ion concentration in SBF and rapid precipitation of bone-like apatite on the composite coating surfaces indicating good bioconductivity of the coatings.
Miriam Rossi - One of the best experts on this subject based on the ideXlab platform.
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Taurolidine Antiadhesive Properties on Interaction with E. coli; Its Transformation in Biological Environment and Interaction with Bacteria Cell Wall
PLOS ONE, 2010Co-Authors: Francesco Caruso, James W. Darnowski, Cristian Opazo, Nina Kishore, Elin S. Agoston, Alexander Goldberg, Miriam RossiAbstract:The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl–4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the Biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a Biological Environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH2 group in the E. coli bacteria cell wall (peptidoglycan) has a negative ΔG value (−38.2 kcal/mol) but a high energy barrier (45.8 kcal/mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methylol-taurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.
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Taurolidine antiadhesive properties on interaction with E. coli; Its transformation in Biological Environment and interaction with bacteria cell wall
PLoS ONE, 2010Co-Authors: Frank Caruso, James W. Darnowski, Cristian Opazo, Nina Kishore, Elin S. Agoston, Alexander Goldberg, Miriam RossiAbstract:The taurine amino-acid derivative, taurolidine, bis-(1,1-dioxoperhydro-1,2,4-thiabiazinyl-4)methane, shows broad antibacterial action against gram-positive and gram-negative bacteria, mycobacteria and some clinically relevant fungi. It inhibits, in vitro, the adherence of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. Taurolidine is unstable in aqueous solution and breaks down into derivatives which are thought to be responsible for the Biological activity. To understand the taurolidine antibacterial mechanism of action, we provide the experimental single crystal X-ray diffraction results together with theoretical methods to characterize the hydrolysis/decomposition reactions of taurolidine. The crystal structure features two independent molecules linked through intermolecular H-bonds with one of them somewhat positively charged. Taurolidine in a Biological Environment exists in equilibrium with taurultam derivatives and this is described theoretically as a 2-step process without an energy barrier: formation of cationic taurolidine followed by a nucleophilic attack of O(hydroxyl) on the exocyclic C(methylene). A concerted mechanism describes the further hydrolysis of the taurolidine derivative methylol-taurultam. The interaction of methylol-taurultam with the diaminopimelic NH(2) group in the E. coli bacteria cell wall (peptidoglycan) has a negative DeltaG value (-38.2 kcal/mol) but a high energy barrier (45.8 kcal/mol) suggesting no reactivity. On the contrary, taurolidine docking into E. coli fimbriae protein, responsible for bacteria adhesion to the bladder epithelium, shows it has higher affinity than mannose (the natural substrate), whereas methylol-taurultam and taurultam are less tightly bound. Since taurolidine is readily available because it is administered in high doses after peritonitis surgery, it may successfully compete with mannose explaining its effectiveness against bacterial infections at laparoscopic lesions.
Xuebin Zheng - One of the best experts on this subject based on the ideXlab platform.
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improved stability of plasma sprayed dicalcium silicate zirconia composite coating
Thin Solid Films, 2006Co-Authors: Xuebin Zheng, Chuanxian DingAbstract:Dicalcium silicate/zirconia composite coatings were produced on Ti–6Al–4V substrates using atmospheric plasma spraying. Different weight ratios of zirconia (50 wt.%, 70 wt.%, 90 wt.%) were mechanically blended with dicalcium silicate (C2S) powders as feedstocks. The composite coatings were immersed in a simulated body fluid (SBF) and a Tris–HCl solution for the in vitro appraisement of stability and long-term performance in a Biological Environment. The ion concentration changes of Ca, Si, and P in SBF and Tris–HCl solution were monitored using inductively-coupled plasma atomic emission spectroscopy (ICP–AES). Compared to the pure C2S coating, our results show that the dissolution rate of the composite coatings is effectively reduced and the stability is improved by the addition of zirconia. The high content of zirconia in the coatings ensures the long-term performance in Biological Environment, while dissolution of C2S in the coatings results in a higher Ca ion concentration in SBF and rapid precipitation of bone-like apatite on the composite coating surfaces indicating good bioconductivity of the coatings.
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Improved stability of plasma-sprayed dicalcium silicate/zirconia composite coating
Thin Solid Films, 2006Co-Authors: Xuebin Zheng, Chuanxian DingAbstract:Dicalcium silicate/zirconia composite coatings were produced on Ti–6Al–4V substrates using atmospheric plasma spraying. Different weight ratios of zirconia (50 wt.%, 70 wt.%, 90 wt.%) were mechanically blended with dicalcium silicate (C2S) powders as feedstocks. The composite coatings were immersed in a simulated body fluid (SBF) and a Tris–HCl solution for the in vitro appraisement of stability and long-term performance in a Biological Environment. The ion concentration changes of Ca, Si, and P in SBF and Tris–HCl solution were monitored using inductively-coupled plasma atomic emission spectroscopy (ICP–AES). Compared to the pure C2S coating, our results show that the dissolution rate of the composite coatings is effectively reduced and the stability is improved by the addition of zirconia. The high content of zirconia in the coatings ensures the long-term performance in Biological Environment, while dissolution of C2S in the coatings results in a higher Ca ion concentration in SBF and rapid precipitation of bone-like apatite on the composite coating surfaces indicating good bioconductivity of the coatings.
