16311-69-6Relevant articles and documents
A stage-specific cancer chemotherapy strategy through flexible combination of reduction-activated charge-conversional core-shell nanoparticles
Han, Lingfei,Wang, Yingming,Huang, Xiaoxian,Liu, Bowen,Hu, Lejian,Ma, Congyu,Liu, Jun,Xue, Jingwei,Qu, Wei,Liu, Fulei,Feng, Feng,Liu, Wenyuan
, p. 6532 - 6549 (2019)
Precision medicine has increased the demand for stage-specific cancer chemotherapy. Drugs with different properties are needed for different stages of tumor development, which is, inducing rapid destruction in the early stage and facilitating deep penetration in the advanced stage. Herein, we report a novel reduction-activated charge-conversional core-shell nanoparticle (CS NP) formula based on ring-closing metathesis of the thiamine disulfide system (TDS) to deliver the chemotherapeutic agent-gambogic acid (GA). Methods: The shell consisted of hyaluronic acid-all-trans retinoid acid with a disulfide bond as the linker (HA-SS-ATRA). The core was selected from poly (γ-glutamic acid) with different grafting rates of the functional group (Fx%) of TDS. GA/CF100%S NPs, with the strongest reduction-responsive drug release, and GA/CF60%S NPs with the strongest penetration have been finally screened. On this basis, a stage-specific administration strategy against a two-stage hepatocellular carcinoma was proposed. Results: The developed CS NPs have been confirmed as inducing reduction-activated charge conversion from about -25 to +30 mV with up to 95% drug release within 48 h. The administration strategy, GA/CF100%S NPs for the early-stage tumor, and sequential administration of GA/CF60%S NPs followed by GA/CF100%S NPs for the advanced-stage tumor, achieved excellent tumor inhibition rates of 93.86±2.94% and 90.76±6.43%, respectively. Conclusions: Our CS NPs provide a novel platform for charge conversion activated by reduction. The stage-specific administration strategy showed great promise for cancer therapy.
Brain targeted prodrug of AMPA receptor synergist and medical purpose thereof
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Paragraph 0103; 0108; 0109, (2017/11/04)
The invention relates to a compound shown by a general formula I, or an isomer, a medicinal salt and a solvate of the compound. The invention also relates to a composition containing the compound shown by the general formula I, or the isomer, the medicinal salt and the solvate of the compound, and a pharmaceutically acceptable carrier, a shaping agent or a diluent. The invention also relates to the compound shown by the general formula I, or the isomer, the medicinal salt and the solvate of the compound, and a purpose for treating glutamic acid hypofunction diseases, neurodegenerative diseases, respiratory depression diseases or symptoms, particularly the purpose used in diseases or symptoms relevant to AMPA receptors. The formula I is shown in the description.
Design, synthesis and biological evaluation of brain-specific glucosyl thiamine disulfide prodrugs of naproxen
Fan, Wei,Wu, Yong,Li, Xian-Kun,Yao, Nian,Li, Xun,Yu, Yong-Guo,Hai, Li
experimental part, p. 3651 - 3661 (2011/11/06)
Glucosyl derivates exhibited favorable distribution to the brain. However, bidirectional transport of glucose transporter 1 might decrease concentrations of the prodrugs in brain before the release of parent drugs. To overcome this defect, glucosyl thiamine disulfide prodrugs 1a-1c incorporating naproxen were designed and synthesized. Furthermore, prodrug 2 and 3 were also prepared as control. The favorable physicochemical properties of these prodrugs were verified by stability and metabolism studies. Results from the in vivo distribution study indicated that 1a-1c, and 1b in particular, significantly increased the level of naproxen in brain when compared to 2 and 3. The study suggested glucosyl thiamine disulfide was a promising carrier to enhance the brain bioavailability of central nervous system active drugs.