The Experts below are selected from a list of 49917 Experts worldwide ranked by ideXlab platform
Samuli Hirsjarvi - One of the best experts on this subject based on the ideXlab platform.
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influence of size surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models
Nanomedicine: Nanotechnology Biology and Medicine, 2013Co-Authors: Samuli Hirsjarvi, Sandrine Dufort, Julien Gravier, Isabelle Texier, Qiao Yan, Jerome Bibette, Lucie Sancey, Veronique JosserandAbstract:Abstract Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic Nanocarriers. Their in vitro and in vivo performance was evaluated as a function of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis methods included complement activation test, particle uptake in macrophage and HEK293(β3) cells and biodistribution studies with tumor-grafted mice by fluorescence imaging. A particular attention was paid to keep the concentration of each nanocarrier and to the amount of fluorescent dye in comparable conditions between the in vitro and in vivo studies. Under these conditions, no significant differences were found among the three tested particle sizes and the two nanocarrier types. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers. Passive accumulation of LNCs and LNEs in different tumor types depended on the degree of tumor vascularization. From the Clinical Editor This study of lipid nanocapsules and lipid nanoemulsions compares their vitro and in vivo performance as a function of size and surface PEG chain length, demonstrating no significant difference among the tested particle sizes. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers.
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Influence of size, surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models
Nanomedicine: Nanotechnology Biology and Medicine, 2013Co-Authors: Samuli Hirsjarvi, Sandrine Dufort, Julien Gravier, Isabelle Texier, Qiao Yan, Jerome Bibette, Lucie Sancey, Veronique Josserand, Catherine Passirani-malleret, Jean-pierre BenoitAbstract:UNLABELLED: Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic Nanocarriers. Their in vitro and in vivo performance was evaluated as a function of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis methods included complement activation test, particle uptake in macrophage and HEK293(β3) cells and biodistribution studies with tumor-grafted mice by fluorescence imaging. A particular attention was paid to keep the concentration of each nanocarrier and to the amount of fluorescent dye in comparable conditions between the in vitro and in vivo studies. Under these conditions, no significant differences were found among the three tested particle sizes and the two nanocarrier types. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers. Passive accumulation of LNCs and LNEs in different tumor types depended on the degree of tumor vascularization. FROM THE CLINICAL EDITOR: This study of lipid nanocapsules and lipid nanoemulsions compares their vitro and in vivo performance as a function of size and surface PEG chain length, demonstrating no significant difference among the tested particle sizes. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers.
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Passive and active tumour targeting with Nanocarriers
Current drug discovery technologies, 2011Co-Authors: Samuli Hirsjarvi, Catherine Passirani, Jean-pierre BenoitAbstract:Nanocarriers can penetrate the tumour vasculature through its leaky endothelium and, in this way, accumulate in several solid tumours. This is called the enhanced permeation and retention (EPR) effect. Together with Nanocarriers whose surface is tailored for prolonged blood circulation times, the concept is referred to as passive targeting. Targeting ligands, which bind to specific receptors on the tumour cells and endothelium, can be attached on the nanocarrier surface. This active targeting increases the selectivity of the delivery of drugs. Passive and active drug targeting with Nanocarriers to tumours reduce toxic side-effects, increase efficacy, and enhance delivery of poorly soluble or sensitive therapeutic molecules. In this review, currently studied and used passive and active targeting strategies in cancer therapy are presented.
Jean-pierre Benoit - One of the best experts on this subject based on the ideXlab platform.
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Influence of size, surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models
Nanomedicine: Nanotechnology Biology and Medicine, 2013Co-Authors: Samuli Hirsjarvi, Sandrine Dufort, Julien Gravier, Isabelle Texier, Qiao Yan, Jerome Bibette, Lucie Sancey, Veronique Josserand, Catherine Passirani-malleret, Jean-pierre BenoitAbstract:UNLABELLED: Lipid nanocapsules (LNCs) and lipid nanoemulsions (LNEs) are biomimetic synthetic Nanocarriers. Their in vitro and in vivo performance was evaluated as a function of their size (25, 50 and 100 nm) and the surface PEG chain length. Analysis methods included complement activation test, particle uptake in macrophage and HEK293(β3) cells and biodistribution studies with tumor-grafted mice by fluorescence imaging. A particular attention was paid to keep the concentration of each nanocarrier and to the amount of fluorescent dye in comparable conditions between the in vitro and in vivo studies. Under these conditions, no significant differences were found among the three tested particle sizes and the two nanocarrier types. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers. Passive accumulation of LNCs and LNEs in different tumor types depended on the degree of tumor vascularization. FROM THE CLINICAL EDITOR: This study of lipid nanocapsules and lipid nanoemulsions compares their vitro and in vivo performance as a function of size and surface PEG chain length, demonstrating no significant difference among the tested particle sizes. Longer PEG chains on the LNE surface provided better stealth properties, whereas PEG modification on the LNC formulations inhibited the production of stable Nanocarriers.
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Passive and active tumour targeting with Nanocarriers
Current drug discovery technologies, 2011Co-Authors: Samuli Hirsjarvi, Catherine Passirani, Jean-pierre BenoitAbstract:Nanocarriers can penetrate the tumour vasculature through its leaky endothelium and, in this way, accumulate in several solid tumours. This is called the enhanced permeation and retention (EPR) effect. Together with Nanocarriers whose surface is tailored for prolonged blood circulation times, the concept is referred to as passive targeting. Targeting ligands, which bind to specific receptors on the tumour cells and endothelium, can be attached on the nanocarrier surface. This active targeting increases the selectivity of the delivery of drugs. Passive and active drug targeting with Nanocarriers to tumours reduce toxic side-effects, increase efficacy, and enhance delivery of poorly soluble or sensitive therapeutic molecules. In this review, currently studied and used passive and active targeting strategies in cancer therapy are presented.
Kai Xiao - One of the best experts on this subject based on the ideXlab platform.
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A drug-specific nanocarrier design for efficient anticancer therapy
Nature communications, 2015Co-Authors: Changying Shi, Dandan Guo, Kai Xiao, Xu Wang, Lili Wang, Juntao LuoAbstract:The drug-loading properties of Nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of Nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing Nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer Nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.
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Telodendrimer-based Nanocarriers for the treatment of ovarian cancer.
Therapeutic delivery, 2013Co-Authors: Kai Xiao, Nell Suby, Kit S LamAbstract:PEG-dendritic block copolymer (telodendrimer) is a unique class of polymers with well-defined structures and tunable aggregation properties, which have been recently developed as novel micelle-based Nanocarriers. This new class of nanocarrier is highly versatile, robust, multifunctional and has many unique properties for drug delivery that are superior to most other Nanocarriers reported in the literature. Reversible crosslinking of micelles is able to minimize the premature drug release during circulation. These crosslinks can be reversed with endogenous and/or exogenous stimuli. To further facilitate the precise delivery of nanoparticle drugs to cancer cells, the nanoparticles surface can be decorated with ovarian cancer targeting ligands. This review is focused on the various strategies used for the design, preparation, pharmacokinetic, biodistribution and preclinical therapeutic applications of telodendrimer-based Nanocarriers for drug delivery in the treatment of ovarian cancer. Lastly, future perspe...
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a novel size tunable nanocarrier system for targeted anticancer drug delivery
Journal of Controlled Release, 2010Co-Authors: Kai Xiao, Juntao Luo, Joyce S Lee, Shirong Pan, Kit S LamAbstract:We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such Nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded Nanocarriers are much more stable than Abraxane (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded Nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded Nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol at equivalent PTX dose in ovarian cancer xenograft model.
Kit S Lam - One of the best experts on this subject based on the ideXlab platform.
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Reversible cross-linked polymeric micelles for drug delivery
Nanoengineered Biomaterials for Advanced Drug Delivery, 2020Co-Authors: Lu Zhang, Kit S LamAbstract:Abstract Biocompatible polymeric Nanocarriers can improve the solubility of many toxic anticancer drugs, prolong the in vivo drug circulation time, and allow preferential accumulation of the drugs at the tumor sites via the enhanced permeability and retention effect. To maximize the stability of the nanocarrier and minimize premature drug release during circulation, intraparticle or intramicellar cross-links can be introduced. In this chapter, we will summarize the development of reversibly cross-linked polymeric Nanocarriers for on-demand drug release in response to single or multiple stimuli at the tumor microenvironment.
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a structure property relationship study of the well defined telodendrimers to improve hemocompatibility of Nanocarriers for anticancer drug delivery
Langmuir, 2014Co-Authors: Changying Shi, Dekai Yuan, Shikha Nangia, Kit S Lam, Juntao LuoAbstract:A series of telodendrimer (a linear polyethyelene glycol-block-dendritic oligo-cholic acid) have been synthesized via a bottom-up approach to optimize the hemocompatibility of the nanocarrier. Numbers of hydrophilic glycerol groups were introduced onto the polar surface of cholic acid to reduce the plasma membrane lytic activity of telodendrimers. An interesting result was observed: only an optimum number of glycerol introduced could reduce the hemolytic properties of the nanocarrier; on the contrary, more glycerols or the amino-glycerol substitution onto cholic acid significantly increased the hemolytic properties of the Nanocarriers. To further elucidate the structure–property relationship, the molecular dynamic approach was used to simulate the conformation of the subunits of telodendrimers with different glycerol substitution, and the binding energies and the polar surface areas of the hairpin conformations were calculated to explain the membrane activities of Nanocarriers. In addition, these telodend...
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Telodendrimer-based Nanocarriers for the treatment of ovarian cancer.
Therapeutic delivery, 2013Co-Authors: Kai Xiao, Nell Suby, Kit S LamAbstract:PEG-dendritic block copolymer (telodendrimer) is a unique class of polymers with well-defined structures and tunable aggregation properties, which have been recently developed as novel micelle-based Nanocarriers. This new class of nanocarrier is highly versatile, robust, multifunctional and has many unique properties for drug delivery that are superior to most other Nanocarriers reported in the literature. Reversible crosslinking of micelles is able to minimize the premature drug release during circulation. These crosslinks can be reversed with endogenous and/or exogenous stimuli. To further facilitate the precise delivery of nanoparticle drugs to cancer cells, the nanoparticles surface can be decorated with ovarian cancer targeting ligands. This review is focused on the various strategies used for the design, preparation, pharmacokinetic, biodistribution and preclinical therapeutic applications of telodendrimer-based Nanocarriers for drug delivery in the treatment of ovarian cancer. Lastly, future perspe...
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a novel size tunable nanocarrier system for targeted anticancer drug delivery
Journal of Controlled Release, 2010Co-Authors: Kai Xiao, Juntao Luo, Joyce S Lee, Shirong Pan, Kit S LamAbstract:We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such Nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded Nanocarriers are much more stable than Abraxane (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded Nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded Nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol at equivalent PTX dose in ovarian cancer xenograft model.
Juntao Luo - One of the best experts on this subject based on the ideXlab platform.
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A drug-specific nanocarrier design for efficient anticancer therapy
Nature communications, 2015Co-Authors: Changying Shi, Dandan Guo, Kai Xiao, Xu Wang, Lili Wang, Juntao LuoAbstract:The drug-loading properties of Nanocarriers depend on the chemical structures and properties of their building blocks. Here we customize telodendrimers (linear dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug-binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of Nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing Nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumour targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer Nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.
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a structure property relationship study of the well defined telodendrimers to improve hemocompatibility of Nanocarriers for anticancer drug delivery
Langmuir, 2014Co-Authors: Changying Shi, Dekai Yuan, Shikha Nangia, Kit S Lam, Juntao LuoAbstract:A series of telodendrimer (a linear polyethyelene glycol-block-dendritic oligo-cholic acid) have been synthesized via a bottom-up approach to optimize the hemocompatibility of the nanocarrier. Numbers of hydrophilic glycerol groups were introduced onto the polar surface of cholic acid to reduce the plasma membrane lytic activity of telodendrimers. An interesting result was observed: only an optimum number of glycerol introduced could reduce the hemolytic properties of the nanocarrier; on the contrary, more glycerols or the amino-glycerol substitution onto cholic acid significantly increased the hemolytic properties of the Nanocarriers. To further elucidate the structure–property relationship, the molecular dynamic approach was used to simulate the conformation of the subunits of telodendrimers with different glycerol substitution, and the binding energies and the polar surface areas of the hairpin conformations were calculated to explain the membrane activities of Nanocarriers. In addition, these telodend...
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a novel size tunable nanocarrier system for targeted anticancer drug delivery
Journal of Controlled Release, 2010Co-Authors: Kai Xiao, Juntao Luo, Joyce S Lee, Shirong Pan, Kit S LamAbstract:We have developed a nanocarrier drug-delivery system based on micelles formed by a new class of well-defined linear PEGylated two-arm oligomer of cholic acids in aqueous solution. By varying the length of the linear PEG chains and the configuration of cholic acid oligomer, one can easily fine-tune the physicochemical properties of the amphiphilic polymers and the resulting micelles. These include particle size, critical micelle concentration, and drug-loading capacity. High level of hydrophobic anticancer drugs such as PTX, etoposide and SN-38 can be readily loaded into such Nanocarriers. The loading capacity of the nanocarrier for PTX (PTX) is extremely high (12.0mg/mL), which is equivalent to 37.5% (w/w) of the total mass of the micelle. PTX-loaded Nanocarriers are much more stable than Abraxane (PTX/human serum albumin nanoaggregate) when stored in bovine serum albumin solution or dog plasma. PTX release profile from the micelles is burst-free and sustained over a period of seven days. The anti-tumor activity of PTX-loaded Nanocarriers against ovarian cancer cell line in vitro, with continuous drug exposure, is similar to Taxol (formulation of PTX dissolved in Cremophor EL and ethanol) or Abraxane. Targeted drug delivery to tumor site with these novel micelles was demonstrated by near infrared fluorescence (NIRF) imaging in nude mice bearing ovarian cancer xenograft. Furthermore, PTX-loaded Nanocarriers demonstrated superior anti-tumor efficacy compared to Taxol at equivalent PTX dose in ovarian cancer xenograft model.
