- Cationic DOPC–Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery
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The ability of a nonviral nucleic acid carrier to deliver its cargo to cells with low associated toxicity is a critical issue for clinical applications of gene therapy. We describe biodegradable cationic DOPC–C12E4 conjugates in which transfection efficiency is based on a Trojan horse strategy. In situ production of the detergent compound C12E4 through conjugate hydrolysis within the acidic endosome compartment was expected to promote endosome membrane destabilization and subsequent release of the lipoplexes into cytosol. The transfection efficiency of the conjugates has been assessed in vitro, and associated cytotoxicity was determined. Cellular uptake and intracellular distribution of the lipoplexes have been investigated. The results show that direct conjugation of DOPC with C12E4 produces a versatile carrier that can deliver both DNA and siRNA to cells in vitro with high efficiency and low cytotoxicity. SAR studies suggest that this compound might represent a reasonable compromise between the membrane activity of the released detergent and susceptibility of the conjugate to degradation enzymes in vitro. Although biodegradability of the conjugates had low impact on carrier efficiency in vitro, it proved critical in vivo. Significant improvement of transgene expression was obtained in the mouse lung tuning biodegradability of the carrier. Importantly, this also allowed reduction of the inflammatory response that invariably characterizes cationic-lipid-mediated gene transfer in animals.
- Pierrat, Philippe,Casset, Anne,Didier, Pascal,Kereselidze, Dimitri,Lux, Marie,Pons, Fran?oise,Lebeau, Luc
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Read Online
- Efficient concrete foam stabilizer and preparation method thereof
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The invention discloses an efficient concrete foam stabilizer and a preparation method thereof, according to the efficient foam stabilizer, polyol is subjected to an esterification reaction to form ester bonds, and the ester bonds are connected with amphiphilic side chains, and the number of the amphiphilic side chains is 3-7; one end of the amphiphilic side chain is a hydrophobic chain segment, and the other end of the amphiphilic side chain is a hydrophilic unit; wherein the hydrophobic chain segment is an alkyl chain (R) with 8-14 carbons, and the hydrophilic unit is 2-10 ethylene oxide units. The efficient concrete foam stabilizer is a multi-chain type surfactant, and the multi-chain type surfactant is hydrolyzed under the alkaline condition to release an air-entraining type surfactant. The efficient concrete foam stabilizer has an excellent effect of stabilizing the air content of concrete, meanwhile, hardened concrete has a better pore structure, and the hardening strength of the concrete cannot be greatly influenced.
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Paragraph 0027; 0055-0056
(2021/07/17)
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- Polyoxyethylene ether carboxylic acid dimeric surfactant type drag reducer as well as preparation method and application thereof
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The invention discloses a polyoxyethylene ether carboxylic acid dimeric surfactant type drag reducer as well as a preparation method and application thereof. The polyoxyethylene ether carboxylic aciddimeric surfactant type drag reducer has a structure formula m=2, 3, 4, and n=1, 2, 3. The drag reducer disclosed by the invention is a dimeric surfactant type drag reducer which has a head group of carboxylic acid, and the head group has the advantages of being very good in temperature resistance, salt resistance, environment protection and the like, and is capable of overcoming influence of a high-salt environment upon drag reduction performance, so that the drag reducer disclosed by the invention is high in drag reduction efficiency, good in shearing resistance, long-lasting and stable in drag reduction rate and good in salt resistance; and polyoxyethylene ether carboxylic acid dimeric surfactants of different mass concentrations are dissolved into water, a drag reduction solution whichis high in drag reduction efficiency, good in shearing resistance, long-lasting and stable in drag reduction rate and good in salt resistance can be prepared without any other compounded chemical reagent, solution blending steps are simple, the drag reducer is very convenient to use, and meanwhile, the salt resistance is greatly improved.
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Paragraph 0105-0107; 0132-0134; 0159-0161
(2019/09/13)
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- Simultaneous Exfoliation and Functionalization of 2H-MoS2 by Thiolated Surfactants: Applications in Enhanced Antibacterial Activity
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Two-dimensional transition metal dichalcogenides (TMDs), such as MoS2, generally exist in two different polymorphic structures, metallic (1T phase) and semiconducting (2H phase). In context of their wide spectrum of applications ranging from electronic to biomedicine, the aspects of ligand conjugation and solution processability are highly significant. In addition, the assessment of their antibacterial property and biocompatibility is equally important to explore their biomedical applications. Here we report a new method for the exfoliation and direct functionalization of 2H-MoS2 using surfactant molecules with thiol functionality. We found that the exfoliated MoS2 using thiolated ligands are functionalized with desired functionality and the processing scheme can be extended to other TMDs. Functionalized 2H-MoS2 exhibits highly enhanced antibacterial efficiency compared to similarly functionalized metallic 1T-MoS2 against pathogenic bacteria. The newly synthesized functionalized 2H-MoS2 exhibits better hemocompatibility, which makes it suitable for in vivo applications. This convenient functionalization method opens the door for many other applications of functionalized semiconducting 2H-MoS2 and other TMDs.
- Karunakaran, Subbaraj,Pandit, Subhendu,Basu, Bikramjit,De, Mrinmoy
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supporting information
p. 12634 - 12644
(2018/10/02)
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- Application of Monodisperse PEGs in Pharmaceutics: Monodisperse Polidocanols
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Polydisperse PEGs are ubiquitously used in pharmaceutical industry and biomedical research. However, the monodispersity in PEGs may play a role in the development of safe and effective PEGylated small molecular drugs. Here, to avoid the polydispersity in polidocanol, the active ingredient in a clinically used drug, a macrocyclic sulfate-based strategy for the efficient and scalable synthesis of monodisperse polidocanols, their sulfates, and their methylated derivatives, was developed. TLC and HPLC analysis indicated a complex mixture in regular polidocanol and high purities in monodisperse polidocanols and their derivatives. Assay on HUVEC, L929, and HePG2 cells showed that monodisperse polidocanols have much higher cytotoxicity and safety than that of regular polidocanol. It was found that the monodispersity of PEGs in polidocanols is crucial for achieving the optimal therapeutic results. Therefore, based on this case study, it would be beneficial to optimize PEGylated small molecular drugs with monodisperse PEGs in pharmaceutical research and development.
- Yu, Zeqiong,Bo, Shaowei,Wang, Huiyuan,Li, Yu,Yang, Zhigang,Huang, Yongzhuo,Jiang, Zhong-Xing
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p. 3473 - 3479
(2017/10/11)
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- PHOSPHOLIPID-DETERGENT CONJUGATES AND USES THEREOF
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The invention relates to novel compounds, in particular novel O-substituted phospholipids that are useful for the in vitro and in vivo delivery of drugs as well as nucleic acids into cells. The invention also relates to pharmaceutical compositions and supramolecular complexes comprising said compounds and the use of these compounds in therapeutic treatment, in particular in gene therapy.
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Page/Page column 79; 80
(2013/03/26)
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- Combinatorial synthesis of PEG oligomer libraries
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A simple chain-extending approach was established for the scale-up of the monoprotected monodisperse PEG diol materials. Reactions of THP-(OCH2CH2)n—OMs (n=4, 8, 12) with a large excess of commercially available H—(OCH2CH2)n—OH (n=1-4) under basic conditions led to THP-(OCH2CH2)n—OH (n=5-15). Similarly, Me-(OCH2CH2)n—OH (n=4-11, 13) were prepared from Me-(OCH2CH2)n—OMs (n=3, 7, 11). For the chain elongation steps, 40-80% yields were achieved through extraction purification. PEG oligomer libraries I and II were generated in 50-95% overall yields by alkylation or acylation of THP-(OCH2CH2)n—OH (n=1-15) followed by deprotection. Alkylation of Me-(OCH2CH2)n—OH (n=1-11, 13) with X—(CH2)m—CO2R (X=Br or OMs) and subsequent hydrolysis led to PEG oligomer library III in 30-60% overall yields. Combinatorial purification techniques were adapted to the larger-scale library synthesis. A total of 498 compounds, each with a weight of 2-5 g and a minimum purity of 90%, were synthesized.
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Page/Page column 9
(2010/02/15)
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- Atmospheric oxidation of poly(oxyethylene) alcohols. Identification of ethoxylated formates as oxidation products and study of their contact allergenic activity
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Ethoxylated alcohols are widely used as surfactants. In the present study we have continued our investigations on the degradation with time upon air exposure of the ethoxylated alcohols at normal storage and handling. As a result, a new group of ethoxylated formates with the general formula C12H25(OCH2CH2)(n)OCHO (n = 0-4) was identified in C12H25(OCH2CH2)5OH stored and handled at room temperature. To facilitate the identification work, reference compounds were synthesized. The formates showed no allergenic activity in the sensitization studies performed. In previous investigations on the same ethoxylated alcohol, we have identified formaldehyde and ethoxylated aldehydes among the oxidation products formed. Formaldehyde is a common contact allergen, and the ethoxylated aldehydes were shown to have a sensitizing capacity of the same magnitude as formaldehyde. The instability of the ethoxylated alcohols and formation of oxidation products may give an allergenic contribution to hand eczema caused by work with water and surfactants. To investigate the clinical significance in man an appropriate diagnostic patch testing in exposed humans is required.
- Bergh, Margareta,Shao, Li Ping,Magnusson, Kerstin,Gaefvert, Elisabeth,Nilsson, J. Lars G.,Karlberg, Ann-Therese
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p. 483 - 488
(2007/10/03)
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- Contact allergens from surfactants. Atmospheric oxidation of polyoxyethylene alcohols, formation of ethoxylated aldehydes, and their allergenic activity
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Ethoxylated surfactants are susceptible to oxidation upon air exposure. We have previously studied the rate of peroxidation and formaldehyde formation in the chemically well-defined ethoxylated alcohol C12H25(OCH2)5OH. Formaldehyde is a common cause of contact allergy. The aim of the present study was to identify other oxidation products that could be formed upon air exposure of the ethoxylated alcohol and to determine their allergenic activity. It was shown that air oxidation of C12H25(OCH2CH2)5OH gave all the theoretically possible aldehydes of the general formula C12H25(OCH:2Ch2)(n)OCH2CHO (n = 0-4) and that the major oxidation product was C12H25(OCH2CH2)4OCH2CHO, dodecyltetraoxyethyleneoxyacetaldehyde. The structure elucidation and synthesis of these aldehydes are here presented for the time. The major aldehyde was shown to be a contact allergen with the same sensitizing capacity as that of formaldehyde. A dose-response relationship was observed in the sensitization studies. The allergens were formed from the surfactant itself and the skin reactions cannot be explained due to any impurities that may be present in a technical quality of the surfactant. Cases of allergic contact dermatitis to ethoxylated surfactants have been reported. To avoid the formation of allergenic oxidation products it is important to control the conditions for storage, handling, and transportation of ethoxylated surfactants.
- Bergh, Margareta,Shao, Li Ping,Hagelthorn, Gunnel,Gaefvert, Elisabeth,Nilsson, J. Lars G.,Karlberg, Ann-Therese
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p. 276 - 282
(2007/10/03)
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