5274-68-0Relevant articles and documents
Cationic DOPC–Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery
Pierrat, Philippe,Casset, Anne,Didier, Pascal,Kereselidze, Dimitri,Lux, Marie,Pons, Fran?oise,Lebeau, Luc
, p. 1771 - 1783 (2016)
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.
Polyoxyethylene ether carboxylic acid dimeric surfactant type drag reducer as well as preparation method and application thereof
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Paragraph 0105-0107; 0132-0134; 0159-0161, (2019/09/13)
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.
Application of Monodisperse PEGs in Pharmaceutics: Monodisperse Polidocanols
Yu, Zeqiong,Bo, Shaowei,Wang, Huiyuan,Li, Yu,Yang, Zhigang,Huang, Yongzhuo,Jiang, Zhong-Xing
, p. 3473 - 3479 (2017/10/11)
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.
