- Naturally derived silicone surfactants based on saccharides and cysteamine
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Silicone surfactants are widely used in many industries and mostly rely on poly(ethylene glycol) (PEG) as the hydrophile. This can be disadvantageous because commercial PEG examples vary significantly in polydispersity—constraining control over surface activity of the surfactant—and there are environmental concerns associated with PEG. Herein, we report a three-step synthetic method for the preparation of saccharide-silicone surfactants using the natural linker, cysteamine, and saccharide lactones. The Piers–Rubinsztajn plus thiol-ene plus amidation process is attractive for several reasons: if employed in the correct synthetic order, it allows for precise tailoring of both hydrophobe and hydrophile; it permits the ready utilization of natural hydrophiles cysteamine and saccharides in combination with silicones, which have significantly better environmental profiles than PEG; and the products exhibit interesting surface activities.
- Brook, Michael A.,Lusterio, Adrien
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- Programmed drug delivery system based on optimized “size decrease and hydrophilicity/hydrophobicity transformation” for enhanced hepatocellular carcinoma therapy of doxorubicin
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Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear “cascading contradictions”, especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized “size decrease and hydrophilicity/hydrophobicity transformation” was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site. Then the degradation of the GNPs triggered by tumor extracellular matrix metalloproteinase-2 (MMP2) led to the release of prodrug Dox-Lac (Mw 898 Da) to facilitate the tumor tissue penetration and cellular uptake. Last, pH-responsive disassociation of Dox-Lac in tumor cells resulted in the free Dox (Mw 543 Da) release to induce toxicity. As expected, GNPs-Dox-Lac achieved superior tumor inhibition rate of 90.8% with low toxicity in vivo, suggesting its potential for enhanced hepatocellular carcinoma (HCC) therapy of doxorubicin in future.
- Liu, Yuanyuan,Li, Lian,Li, Lijia,Zhou, Zhou,Wang, Fengling,Xiong, Xiaofeng,Zhou, Rui,Huang, Yuan
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p. 1111 - 1122
(2018/03/23)
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- Glycosylated Reversible Addition-Fragmentation Chain Transfer Polymers with Varying Polyethylene Glycol Linkers Produce Different Short Interfering RNA Uptake, Gene Silencing, and Toxicity Profiles
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Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work, we report the design, synthesis, and biological evaluation of a novel polymeric delivery vector incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of carbohydrate functionality and its distance from the polymer backbone is conducted using reversible addition-fragmentation chain transfer polymerization and postpolymerization modification.
- Williams, Elizabeth G. L.,Hutt, Oliver E.,Hinton, Tracey M.,Larnaudie, Sophie C.,Le, Tam,Macdonald, James M.,Gunatillake, Pathiraja,Thang, San H.,Duggan, Peter J.
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p. 4099 - 4112
(2017/12/26)
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- Compound with antitumor activity, and preparation method and application thereof
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The invention provides a compound with antitumor activity, and a preparation method and application thereof, and relates to the technical field of chemical compounding drugs. The compound is of a structure shown as a formula (I) or (II). The stimuli-responsive self-assembly unimolecular compound with the antitumor activity is prepared through condensation reaction between hepatic-targeting water-soluble lactose and a platinum (IV) compound. The compound has the advantages that hepatic-targeting water-soluble lactose molecules are introduced, water-solubility of the platinum (IV) compound is improved, and hydrophilic-lyophobic balance is achieved, so that the self-assembly unimolecular platinum (IV) compound is formed, cytotoxicity of the platinum (IV) compound is reduced, a compounded tetravalence platinum prodrug has amphipathy, and accumulation degree of hepatoma cells can be increased; due to platinum, activation and release of the platinum compound are benefited under the conditions of external photostimulation or intracellular reduction, and accordingly, high antitumor activity is achieved.
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Paragraph 0078; 0082; 0084; 0090; 0098; 0106; 0114; 0122
(2017/12/28)
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- A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy
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Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy.
- Mou, Quanbing,Ma, Yuan,Zhu, Xinyuan,Yan, Deyue
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- Preparation and characterization of galactosylated alginate-chitosan oligomer microcapsule for hepatocytes microencapsulation
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Galactosylated alginate (GA)-chitosan oligomer microcapsule was prepared to provide a sufficient mechanical stability, a selective permeability and an appropriate three-dimensional (3D) microenvironment for hepatocytes microencapsulation. The microcapsule has a unique asymmetric membrane structure, with a dense layer located in the inner surface and gradually decreasing toward the outside surface. The stable microcapsule was obtained when GA lower than 50%, while the permeability was increased with increasing of GA. A balance between mechanical stability and permeability was achieved through modulating membrane porosity and thickness. The optimal microcapsule displays a selective permeability allowing efficient transport of human serum albumin while effectively blocking immunoglobulin G. Hepatocytes exhibited high and long term viability (>92%), proliferability, multicellular spheroid morphology, and enhancement of liver-specific functions in the microcapsule wherein galactose moieties present chemical cues to support cell-matrix interactions while the 3D structure of the microcapsule behaves physical cues to facilitate cell-cell interactions.
- Tian, Meng,Han, Bo,Tan, Hong,You, Chao
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p. 502 - 511
(2014/07/22)
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- Direct synthesis and aqueous solution properties of well-defined cyclic sugar methacrylate polymers
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The direct synthesis and aqueous solution properties of well-defined cyclic sugar methacrylate polymers were presented. The first step in the sugar monomer synthesis involved the preparation of lactobionolactone from lactobionic acid. The residual copper contents of the purified sugar polymers were determined by inductively coupled plasma atomic emission spectroscopy.
- Narain, Ravin,Armes, Steven P.
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p. 4675 - 4678
(2007/10/03)
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- Vesicles and other supramolecular systems from biocompatible synthetic glycolipids with hydrocarbon and/or fluorocarbon chains
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A series of double-tailed hydrocarbon and/or fluorocarbon glycolipids derived from galactose and glucose have been prepared. These compounds were obtained upon opening a lactono- and maltonolactone moiety by the amino group of either a glycine, glycylglycine or lysine residue. The carboxyl terminus of the glycyl and glycylglycine conjugates was further reacted with the appropriate double-tailed amine. In the case of lysine, the lactonamide conjugate was functionalized with a hydrocarbon and/or fluorocarbon fatty amine and acid, respectively. The ability of such glycolipids to disperse in water, the morphology of self-assemblies formed and the stability of the supramolecular structure obtained were shown to depend on the presence or absence and on the nature of the aminoacid spacer. Most of the compounds described were shown by conventional techniques (TEM, Cryo-TEM, LLS, etc.) to produce stable vesicular systems.
- Guedj,Pucci,Zarif,Coulomb,Riess,Pavia
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p. 153 - 173
(2007/10/02)
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