The Experts below are selected from a list of 76815 Experts worldwide ranked by ideXlab platform
Kazunori Kataoka - One of the best experts on this subject based on the ideXlab platform.
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effect of integrin targeting and peg shielding on polyplex micelle internalization studied by live cell imaging
Journal of Controlled Release, 2011Co-Authors: Frauke Martina Mickler, Kazunori Kataoka, Nobuhiro Nishiyama, Kanjiro Miyata, Yelena Vachutinsky, Makoto Oba, Christoph Brauchle, Nadia RuthardtAbstract:α(v)β(3) and α(v)β(5) integrins are attractive target structures for cancer therapy as they are upregulated in tumor and tumor associated host cells and play a pivotal role for tumor growth and metastasis. Gene vectors such as polyplex Micelles consisting of thiolated PEG-block-poly(lysine) copolymers complexed with plasmid DNA can be targeted to these specific integrins by equipment with a cyclic RGD peptide. In this study, we analyzed the effect of the RGD ligand on micelle endocytosis by comparing fluorescently labeled, targeted and untargeted Micelles in live-cell imaging experiments with highly sensitive fluorescence microscopy and flow cytometry. Two micelle types with 12 kDa (PEG12) and 17 kDa (PEG17) PEG shell layers were examined to evaluate the influence of surface shielding on the internalization characteristics. Our results reveal three major effects: First, the RGD ligand accelerates the internalization of Micelles into integrin expressing HeLa cells without changing the uptake pathway of the Micelles. Both targeted as well as untargeted Micelles are predominantly internalized via clathrin mediated endocytosis. Second, the PEG shielding of Micelles has an important effect on their targeting specificity. At high PEG shielding selective endocytosis of integrin targeted Micelles occurs, whereas at low PEG shielding targeted and untargeted Micelles show comparable internalization. In addition, PEG17 RGD(+) Micelles induce the highest reporter gene expression. Third, our data demonstrate a clear influence of the applied micelle dose on the internalization of integrin targeted Micelles. We propose that PEG17 shielded Micelles equipped with a cyclic RGD ligand are the favored system of choice for clinical therapy as they exhibit higher transgene expression, a higher specificity for integrin-dependent endocytosis compared to PEG12 shielded Micelles, and are functional at low doses as well.
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preclinical and clinical studies of anticancer agent incorporating polymer Micelles
Cancer Science, 2009Co-Authors: Yasuhiro Matsumura, Kazunori KataokaAbstract:The size of anticancer agent-incorporating Micelles can be controlled within the diameter range of 20-100 nm to ensure that they do not penetrate normal vessel walls. With this development, it is expected that the incidence of drug-induced side-effects may be decreased owing to the reduced drug distribution in normal tissue. Micelle systems can also evade non-specific capture by the reticuloendothelial system because the outer shell of a micelle is covered with polyethylene glycol. Consequently, a polymer micelle carrier can be delivered selectively to a tumor by utilizing the enhanced permeability and retention effect. Moreover, a water-insoluble drug can be incorporated into polymer Micelles. Presently, several anticancer agent-incorporating micelle carrier systems are under preclinical and clinical evaluation. Furthermore, nucleic acid-incorporating micelle carrier systems are also being developed.
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polyion complex Micelles of pdna with acetal poly ethylene glycol poly 2 dimethylamino ethyl methacrylate block copolymer as the gene carrier system physicochemical properties of Micelles relevant to gene transfection efficacy
Biomacromolecules, 2004Co-Authors: Daisuke Wakebayashi, Nobuhiro Nishiyama, Keiji Itaka, Kanjiro Miyata, Yuichi Yamasaki, Atsushi Harada, Hiroyuki Koyama, Yukio Nagasaki, Kazunori KataokaAbstract:An acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (acetal-PEG-PAMA) block copolymer spontaneously associated with plasmid DNA (pDNA) to form water-soluble complexes (polyion complex micelle: PIC micelle) in aqueous solution. Physicochemical characteristics and transfection efficiency of the PIC Micelles thus prepared were studied here, focusing on the residual molar mixing ratio (N/P ratio) of AMA units in acetal-PEG-PAMA to the phosphate units in pDNA. With the N/P ratio increasing to unity, acetal-PEG-PAMA cooperatively formed complex Micelles with pDNA through electrostatic interaction, allowing pDNA to condense effectively. Dynamic light scattering measurements revealed that the PIC micelle at N/P ≥ 3 had a constant size of approximately 90−100 nm. Eventually, acetal-PEG-PAMA/pDNA Micelles underwent no precipitation even after long-term storage for more than 1 month at all N/P ratios. The PIC Micelles were stable even in the presence of excess polyanions, poly(vinyl sulfate), ...
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long circulating poly ethylene glycol poly d l lactide block copolymer Micelles with modulated surface charge
Journal of Controlled Release, 2001Co-Authors: Yuji Yamamoto, Yukio Nagasaki, Yukio Kato, Yuichi Sugiyama, Kazunori KataokaAbstract:Reactive polymeric Micelles consisting of an alpha-acetal-poly(ethylene glycol)-poly(D,L-lactide) block copolymer (acetal-PEG-PDLLA) with a narrow size distribution were prepared in this study to conjugate small peptidyl ligands, tyrosine (Tyr) and tyrosyl-glutamic acid (Tyr-Glu), through reductive amination after converting the alpha-acetal group to an aldehyde group, allowing modulation of the surface charge of the Micelles from neutral (Tyr-) to anionic (Tyr-Glu-). Both of these Micelles showed a significantly long circulating time in the blood compartment with 25% of injected dose still circulating even at 24 h. Further, an appreciably lowered uptake into the liver and spleen was demonstrated for the anionic Tyr-Glu-conjugated PEG-PDLLA micelle compared with a neutral Tyr-conjugated micelle, suggesting a substantial role of the slight anionic charge on the micelle surface in avoiding non-specific organ uptake. Stability of the micelle form in the blood compartment was directly observed for the Tyr-PEG-PDLLA micelle by a gel filtration assay of a plasma sample collected from the micelle-injected mice at 24 h. These results demonstrated that a surface-modulated PEG-PDLLA micelle with a suitable size and a narrowly distributed nature has promising potential as a long-circulating carrier system with desirable biocompatibility and biofunctionality.
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doxorubicin loaded poly ethylene glycol poly β benzyl l aspartate copolymer Micelles their pharmaceutical characteristics and biological significance
Journal of Controlled Release, 2000Co-Authors: Kazunori Kataoka, Masayuki Yokoyama, Kazuya Okamoto, Shigeto Fukushima, Tsuyoshi Matsumoto, Teruo Okano, Yasuhisa Sakurai, Glen S KwonAbstract:Abstract Doxorubicin (DOX) was physically loaded into Micelles prepared from poly(ethylene glycol)–poly(β-benzyl- l -aspartate) block copolymer (PEG–PBLA) by an o/w emulsion method with a substantial drug loading level (15 to 20 w/w%). DOX-loaded Micelles were narrowly distributed in size with diameters of approximately 50–70 nm. Dimer derivatives of DOX as well as DOX itself were revealed to be entrapped in the micelle, the former seems to improve micelle stability due to its low water solubility and possible interaction with benzyl residues of PBLA segments through π–π stacking. Release of DOX compounds from the Micelles proceeded in two stages: an initial rapid release was followed by a stage of slow and long-lasting release of DOX. Acceleration of DOX release can be obtained by lowering the surrounding pH from 7.4 to 5.0, suggesting a pH-sensitive release of DOX from the Micelles. A remarkable improvement in blood circulation of DOX was achieved by use of PEG–PBLA micelle as a carrier presumably due to the reduced reticuloendothelial system uptake of the Micelles through a steric stabilization mechanism. Finally, DOX loaded in the micelle showed a considerably higher antitumor activity compared to free DOX against mouse C26 tumor by i.v. injection, indicating a promising feature for PEG–PBLA micelle as a long-circulating carrier system useful in modulated drug delivery.
Adi Eisenberg - One of the best experts on this subject based on the ideXlab platform.
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loading and release mechanisms of a biocide in polystyrene block poly acrylic acid block copolymer Micelles
Journal of Physical Chemistry B, 2008Co-Authors: Renata Vyhnalkova, Adi Eisenberg, Theo G M Van De VenAbstract:The kinetics of loading of polystyrene197-block-poly(acrylic acid)47 (PS197-b-PAA47) Micelles, suspended in water, with thiocyanomethylthiobenzothiazole biocide and its subsequent release were investigated. Loading of the Micelles was found to be a two-step process. First, the surface of the PS core of the Micelles is saturated with biocide, with a rate determined by the transfer of solid biocide to Micelles during transient micelle−biocide contacts. Next, the biocide penetrates as a front into the Micelles, lowering the Tg in the process (non-Fickian case II diffusion). The slow rate of release is governed by the height of the energy barrier that a biocide molecule must overcome to pass from PS into water, resulting in a uniform biocide concentration within the micelle, until Tg is increased to the point that diffusion inside the Micelles becomes very slow. Maximum loading of biocide into Micelles is ∼30% (w/w) and is achieved in 1 h. From partition experiments, it can be concluded that the biocide has a...
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block copolymer Micelles as delivery vehicles of hydrophobic drugs micelle cell interactions
Journal of Drug Targeting, 2006Co-Authors: Radoslav Savic, Adi Eisenberg, Dusica MaysingerAbstract:One-third of drugs in development are water insoluble and one-half fail in trials because of poor pharmacokinetics. Block copolymer Micelles are nanosized particles that can solubilize hydrophobic drugs and alter their kinetics in vitro and in vivo. However, block copolymer Micelles are not solely passive drug containers that simply solubilize hydrophobic drugs; cells internalize Micelles. To facilitate the development of advanced, controlled, micellar drug delivery vehicles, we have to understand the fate of Micelles and micelle-incorporated drugs in cells and in vivo. With micelle-based drug formulations recently reaching clinical trials, the impetus for answers is ever so strong and detailed studies of interactions of Micelles and cells are starting to emerge. Most notably, the question arises: Is the internalization of block copolymer Micelles carrying small molecular weight drugs an undesired side effect or a useful means of improving the effectiveness of the incorporated drugs?
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polycaprolactone b poly ethylene oxide copolymer Micelles as a delivery vehicle for dihydrotestosterone
Journal of Controlled Release, 2000Co-Authors: Christine Allen, Dusica Maysinger, Jeannie Han, Adi EisenbergAbstract:Block copolymer Micelles formed from copolymers of poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) were investigated as a drug delivery vehicle for dihydrotestosterone (DHT). The physical parameters of the PCL-b-PEO micelle-incorporated DHT were measured, including the loading capacity of the Micelles for DHT, the apparent partition coefficient of DHT between the Micelles and the external medium and the kinetics of the release of DHT from the micelle solution. The MTT survival assay was used to assess the in vitro biocompatibility of PCL-b-PEO Micelles in HeLa cell cultures. The biological activity of the micelle-incorporated DHT was evaluated in HeLa cells which had been co-transfected with the expression vectors for the androgen receptor and the MMTV-LUC reporter gene. The PCL-b-PEO Micelles were found to have a high loading capacity for DHT and the release profile of the drug from the micelle solution was found to be a slow steady release which continued over a 1-month period. The biological activity of the micelle-incorporated DHT was found to be fully retained.
Glen S Kwon - One of the best experts on this subject based on the ideXlab platform.
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doxorubicin loaded poly ethylene glycol poly β benzyl l aspartate copolymer Micelles their pharmaceutical characteristics and biological significance
Journal of Controlled Release, 2000Co-Authors: Kazunori Kataoka, Masayuki Yokoyama, Kazuya Okamoto, Shigeto Fukushima, Tsuyoshi Matsumoto, Teruo Okano, Yasuhisa Sakurai, Glen S KwonAbstract:Abstract Doxorubicin (DOX) was physically loaded into Micelles prepared from poly(ethylene glycol)–poly(β-benzyl- l -aspartate) block copolymer (PEG–PBLA) by an o/w emulsion method with a substantial drug loading level (15 to 20 w/w%). DOX-loaded Micelles were narrowly distributed in size with diameters of approximately 50–70 nm. Dimer derivatives of DOX as well as DOX itself were revealed to be entrapped in the micelle, the former seems to improve micelle stability due to its low water solubility and possible interaction with benzyl residues of PBLA segments through π–π stacking. Release of DOX compounds from the Micelles proceeded in two stages: an initial rapid release was followed by a stage of slow and long-lasting release of DOX. Acceleration of DOX release can be obtained by lowering the surrounding pH from 7.4 to 5.0, suggesting a pH-sensitive release of DOX from the Micelles. A remarkable improvement in blood circulation of DOX was achieved by use of PEG–PBLA micelle as a carrier presumably due to the reduced reticuloendothelial system uptake of the Micelles through a steric stabilization mechanism. Finally, DOX loaded in the micelle showed a considerably higher antitumor activity compared to free DOX against mouse C26 tumor by i.v. injection, indicating a promising feature for PEG–PBLA micelle as a long-circulating carrier system useful in modulated drug delivery.
Gle S Kwo - One of the best experts on this subject based on the ideXlab platform.
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doxorubicin loaded poly ethylene glycol poly β benzyl l aspartate copolymer Micelles their pharmaceutical characteristics and biological significance
Journal of Controlled Release, 2000Co-Authors: Kazunori Kataoka, Masayuki Yokoyama, Kazuya Okamoto, Shigeto Fukushima, Tsuyoshi Matsumoto, Teruo Okano, Yasuhisa Sakurai, Gle S KwoAbstract:Doxorubicin (DOX) was physically loaded into Micelles prepared from poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) block copolymer (PEG-PBLA) by an o/w emulsion method with a substantial drug loading level (15 to 20 w/w%). DOX-loaded Micelles were narrowly distributed in size with diameters of approximately 50-70 nm. Dimer derivatives of DOX as well as DOX itself were revealed to be entrapped in the micelle, the former seems to improve micelle stability due to its low water solubility and possible interaction with benzyl residues of PBLA segments through pi-pi stacking. Release of DOX compounds from the Micelles proceeded in two stages: an initial rapid release was followed by a stage of slow and long-lasting release of DOX. Acceleration of DOX release can be obtained by lowering the surrounding pH from 7.4 to 5.0, suggesting a pH-sensitive release of DOX from the Micelles. A remarkable improvement in blood circulation of DOX was achieved by use of PEG-PBLA micelle as a carrier presumably due to the reduced reticuloendothelial system uptake of the Micelles through a steric stabilization mechanism. Finally, DOX loaded in the micelle showed a considerably higher antitumor activity compared to free DOX against mouse C26 tumor by i.v. injection, indicating a promising feature for PEG-PBLA micelle as a long-circulating carrier system useful in modulated drug delivery.
John E Straub - One of the best experts on this subject based on the ideXlab platform.
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aerosol ot surfactant forms stable reverse Micelles in apolar solvent in the absence of water
Journal of Physical Chemistry B, 2019Co-Authors: Ryo Urano, George A Pantelopulos, John E StraubAbstract:Normal micelle aggregates of amphiphilic surfactant in aqueous solvents are formed by a process of entropically driven self-assembly. The self-assembly of reverse Micelles from amphiphilic surfactant in a nonpolar solvent in the presence of water is considered to be an enthalpically driven process. Although the formation of normal and reverse surfactant Micelles has been well characterized in theory and experiment, the nature of dry micelle formation, from amphiphilic surfactant in a nonpolar solvent in the absence of water, is poorly understood. In this study, a theory of dry reverse micelle formation is developed. Variation in free energy during micelle assembly is derived for the specific case of aerosol-OT surfactant in isooctane solvent using atomistic molecular dynamics simulation analyzed using the energy representation method. The existence and thermodynamic stability of dry reverse Micelles of limited size are confirmed. The abrupt occurrence of monodisperse aggregates is a clear signature of a critical micelle concentration, commonly observed in the formation of normal surfactant Micelles. The morphology of large dry Micelles provides insight into the nature of the thermodynamic driving forces stabilizing the formation of the surfactant aggregates. Overall, this study provides detailed insight into the structure and stability of dry reverse Micelles assembly in a nonpolar solvent.
