查找使用阿拉丁产品的科研文献

Assessment on the binding characteristics of dasatinib, a tyrosine kinase inhibitor to calf thymus DNA: insights from multi-spectroscopic methodologies and molecular docking as well as DFT calculation

Yu-Jie Luo,Bao-Li Wang,Song-Bo Kou,Zhen-Yi Lin,Kai-Li Zhou,Yan-Yue Lou,Jie-Hua Shi

The binding characteristics of calf thymus DNA (ct-DNA) with dasatinib (DSTN), a tyrosine kinase inhibitor was assessed through multi-spectroscopic methodologies and viscosity measurement combined with molecular docking as well as DFT calculation to understand the binding mechanism, affinity of DSTN onto ct-DNA, effect of DSTN on ct-DNA conformation, and among others. The results confirmed DSTN bound onto ct-DNA, leading to forming the DSTN–ct-DNA complex with the binding constant of 4.82 × 103 M−1 at 310 K. DSTN preferentially inserted to the minor groove of ct-DNA with rich A-T region, that was the binding mode of DSTN onto ct-DNA was groove binding. The enthalpic change (ΔH0) and entropic change (ΔS0) during the binding process of DSTN with ct-DNA were 128.9 kJ mol−1 and 489.2 J mol−1 K−1, respectively, confirming clearly that the association of DSTN with ct-DNA was an endothermic process and the dominative driven-force was hydrophobic interaction. Meanwhile, the results also indicated that there was a certain extent of electrostatic force and hydrogen bonding, but they maybe play an auxiliary role. The CD measurement results confirmed the alteration in the helical configuration of ct-DNA but almost no change in the base stacking after binding DSTN. The results revealed that there was the obvious change in the conformation, the dipole moment, and the atomic charge distribution of DSTN in the B-DNA complexes, compared with free DSTN, to satisfy the conformational adaptation. From the obtained fronitier molecular orbitals of DSTN, it can be inferred that the nature of DSTN alters with the change of the environment around DSTN.Communicated by Ramaswamy H. Sarma

Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization

Qingqing Li,Xianwei Yang,Peipei Zhang,Fei Mo,Peiru Si,Ximeng Kang,Menghan Wang,Jiye Zhang

Corneal neovascularization (CNV) is one of the most important causes of visual impairment worldwide. Dasatinib, a poorly water-soluble tyrosine kinase inhibitor with dual Src family kinase and platelet derived growth factor receptor inhibiting capability, has great potential in the treatment of CNV. In this study, dasatinib was successfully encapsulated into a nanostructured lipid carrier (Dasa-NLC) and the size was approximately 78 nm with a small polydispersity index. The NLC increased the solubility of dasatinib by more than 1220 times, sustained the drug release, reduced the ocular toxicity and facilitated its penetration into the cornea. Dasa-NLC significantly inhibited the proliferation, migration and tube formation of HUVEC cells, the three most important angiogenesis-related cellular changes of the CNV. Next, the in vivo anti-CNV effect of Dasa-NLC was evaluated using an alkaline burned mice CNV model, in which the development of the CNV and pathological changes of the cornea were significantly inhibited. The immunohistochemistry analysis indicated that Dasa-NLC could inhibit both the expression and activation of Src family kinase, a key component in the angiogenesis cascade. Therefore, Dasa-NLC showed considerable promise in the treatment of CNV.

Dasatinib Nanoemulsion and Nanocrystal for Enhanced Oral Drug Delivery

Chuanqi Wang,Manting Wang,Peng Chen,Jiexin Wang,Yuan Le

In this work, dasatinib (DAS) nanoemulsion and nanocrystal are produced by high-gravity technology that approaches to practical mass production. The drug nanoformulations were systematically characterized and evaluated. At a low high-gravity level (β) = 47, nanoemulsion droplets were 16.15 ± 0.42 nm with a PDI of 0.122 ± 0.021. The nanoemulsion’s size and active pharmaceutical ingredient (API) content remained stable at long-term (4 months) freeze–thaw and dilution experiments. At a high β = 188, the as-prepared nanocrystal was lamellar with a short diameter of about 200 nm and a long diameter of about 750 nm. In vitro performances demonstrated the nanoemulsion displayed higher cytotoxicity on MDA-MB-231 tumor cells, Caco-2 cell permeability and drug release than that of the nanocrystal, indicating that nanoemulsion should be an ideal alternative for dasatinib oral administration.Keywords:dasatinib;nanoemulsion;nanocrystal;high-gravity technology;in vitro performances

Carrier-free prodrug nanoparticles based on dasatinib and cisplatin for efficient antitumor in vivo

Lu Yang,Jiaxi Xu,Zheng Xie,Faquan Song,Xin Wang,Rupei Tang

Carrier-free drug self-delivery systems consisting of amphiphilic drug-drug conjugate (ADDC) with well-defined structure and nanoscale features have drawn much attention in tumor drug delivery. Herein, we report a simple and effective strategy to prepare ADDC using derivatives of cisplatin (CP) and dasatinib (DAS), which further self-assembled to form reduction-responsive nanoparticles (CP-DDA NPs). DAS was modified with succinic anhydride and then connected with CP derivative by ester bonds. The size, micromorphology and in vitro drug release of CP-DDA NPs were characterized. The biocompatibility and bioactivity of these carrier-free nanoparticles were then investigated by HepG2 cells and H22-tumor bearing mice. In vitro and in vivo experiments proved that CP-DDA NPs had excellent anti-tumor activity and significantly reduced toxicities. This study provides a new strategy to design the carrier-free nanomedicine composed of CP and DAS for synergistic tumor treatment.

pH-Sensitive blue-green dual-emission carbon dots for dasatinib detection

Yujia Zhong,Tongyan Bao,Xinghang Yin,Qunfen Deng,Yu Zhang,Tingfang Wu,Rui Yang

A dual-signal fluorescent probe with 2-aminoterephthalic acid and p-aminosalicylic acid as precursors was presented for the sensing of anticancer drug dasatinib (DAS). Blue-green dual-emission carbon dots (BG-CDs) with 450 nm and 520 nm fluorescence emission were synthesized by a one-step hydrothermal method. Based on the inner filter effect (IFE), DAS could result in dual-peak quenching of BG-CDs. And the fluorescence intensity of dual-peak BG-CDs gradually decreased with the increase of DAS concentration. There was a good linear relationship between the quenching difference values of dual-peak fluorescence intensity and the concentration of DAS in the range of 2.42–150 μmol·L −1 , and the limit of detection was 0.81 μmol·L −1 . Meanwhile, the BG-CDs could also be employed for the determination of pH between 3.0 and 6.5 with good reversibility. Compared with other traditional single-signal detection strategies, the dual-signal method yielded more accurate and reliable results.

Biomineralization-inspired dasatinib nanodrug with sequential infiltration for effective solid tumor treatment

Yanhong Liu,Lingchao Li,Jiyong Liu,Mengnan Yang,Honglan Wang,Xuxin Chu,Jianping Zhou,Meirong Huo,Tingjie Yin

The complex blood environment, heterogenic enhanced permeability and retention (EPR) effect, and dense matrix comprise the primary “leakage obstacles” impeding specific accumulation and penetration of nanodrugs against solid tumors, thus forming a key bottleneck for their clinical application. Herein, we present a biomineralization-inspired dasatinib (DAS) nanodrug (CIPHD/DAS) that sequentially permeates all of the abovementioned hindrances for efficient treatment of solid tumors. CIPHD/DAS exhibited a robust hybrid structure constructed from an iRGD-modified hyaluronic acid-deoxycholic acid organic core and a calcium phosphate mineral shell. In vitro and in vivo data demonstrated the mechanism of sequential tumoral infiltration was based on mineral-stiffened blood circulation with decreased premature drug leakage, iRGD-endowed tumor-specific transendothelial transport for “first-order promotion of accumulation” and DAS-mediated restoration of fibrotic stromal homeostasis for “second-order promotion of penetration”. Resultantly, CIPHD/DAS showed remarkable distal drug availability in desmoplastic 4T1/CAFs orthotropic mouse models and significantly suppressed tumor growth and metastasis. This optimized strategy with sequential permeabilization of the capital “leakage obstacles” validates a promising paradigm to conquer the “impaired delivery and penetration” associated bottleneck of nanodrugs in the clinical treatment of solid tumors.

Dasatinib and erianin co-loaded ion-responsive in-situ hydrogel for effective treatment of corneal neovascularization

Jiaxing Lei,Lei Wang,Chen Yang,Dongdong Li,Jiaxue Zhang,Jia Ma,Peipei Zhang,Qingqing Li,Jiye Zhang

Corneal neovasularization (CNV) is one of the leading causes for visual impairment. Dasatinib is a multi-target tyrosine kinase inhibitor, which can inhibit both platelet derived growth factor receptor and Src family kinases. Erianin exhibits excellent anti-inflammatory and anti-angiogenic effects. In this study, dasatinib and erianin were found to synergically inhibit the proliferation, migration and tube formation of Ea.hy926 cells, the three most important cellular processes of CNV. Next, dasatinib and erianin were co-encapsulated in nanostructured lipid carriers (dasa-eri-NLC), which increased the solubility of dasatinib by about 1790 times, increased the solubility of erianin by about 3 times. To improve its retention time on the ocular surface, dasa-eri-NLC was mixed with gellan gum (dasa-eri-NLC-gel), which achieved a sol-gel transformation when got in contact with tears. The dasa-eri-NLC-gel exhibited good rheological properties with shear thinning properties, extended the ocular residence time by more than 6 times, sustained the drug release, improved the corneal permeability of drug and exhibited good biocompatibility. Finally, the in vivo anti-CNV effect was evaluated in an alkaline burned mouse model of CNV, in which, the dasa-eri-NLC-gel significantly impeded the development and pathological changes of CNV, inhibited the expression of TNF-α, VEGF-A, HIF-1α, Src, p Src in the cornea. In summary, dasa-eri-NLC-gel safely and efficiently delivered dasatinib and erianin to the cornea and exhibited significantly anti-CNV effect via inhibiting various angiogenesis related cytokines or factors. Dasa-eri-NLC-gel showed a great promise for the treatment of CNV and our study laid a solid foundation for future clinical transformation.

Scale-up microreactor coupling binary surfactants for high-throughput preparation of flaky dasatinib nanocrystals

Fei Yuan,Yuzhong Sun,Jiayi Guo,Yimin Wei,Su Wang,Shuangfei Zhao,Ruiyan Sun,Wei He,Ning Zhu,Yuguang Li,Kai Guo

Background Traditional methods for nanocrystal preparation often suffer from limitations such as poor control over particle size and morphology, low yield and instability. Methods In this study, we developed a novel microreactor technique for the efficient preparation of dasatinib nanocrystals. The microreactor employed was equipped with a circular hole baffle to enhance mixing efficiency. The solvent-antisolvent process was optimized by systematically varying the solvent-to-antisolvent ratio, flow rate, and initial concentration of dasatinib. A binary surfactant system (SDBS/BS-12) was introduced in the anti-solvent phase to further improve the nanocrystal properties. Significant Findings The optimized experimental conditions led to the successful preparation of dasatinib nanocrystals with exceptional properties. The nanocrystals exhibited an average particle size of 85 nm, a zeta potential of 47.5 mV, and a polydispersity index of 0.566, indicating superior dispersion and stability. Compared to conventional methods, the binary surfactant system resulted in a remarkable 6.5–12 times enhancement in nanocrystal shrinkage. The precise control over mixing dynamics within the microreactor enabled the production of high-quality nanocrystals with tailored properties. Furthermore, the simplicity, efficiency, and tunability of the proposed method suggests its potential for scale-up towards high-throughput nanoparticle preparation, broadening its application prospects in various fields.

A validated UPLC–MS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma

Jing Zeng,Hua lin Cai,Zhi ping Jiang,Qing Wang,Yan Zhu,Ping Xu,Xie lan Zhao

A sensitive, rapid, simple and economical ultra-performance liquid chromatography–tandem mass spectrometric method (UPLC–MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate) and B (organic phase: acetonitrile) (A:B=40:60, v/v). The flow rate was 0.25   mL/min and the total run time was 6   min. The multiple reaction monitoring (MRM) transitions, m/z 494.5→394.5 for imatinib, 488.7→401.5 for dasatinib, 530.7→289.5 for nilotinib and 528.5→403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6–5250.0   ng/mL for imatinib, 2.0–490.0   ng/mL for dasatinib, and 2.4–4700.0   ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLC–MS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 −1889T>C or SLCO1B3 699G>A genotypes ( P >0.05). This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors (TKIs).

Dasatinib self-assembled nanoparticles decorated with hyaluronic acid for targeted treatment of tumors to overcome multidrug resistance

Yawen Zhang,Xiangle Zeng,Hairong Wang,Ranran Fan,Yike Hu,Xuejie Hu,Jianchun Li

Simultaneous determination of paclitaxel and dasatinib in rat plasma and pharmacokinetic study on liquid chromatography-tandem mass spectrometry

Yuan Liang,Jun Yin,Yu Yang,Ruiyan Huang,Penghui Hu,Chang Shu

For most cancers, drugs in combination with chemotherapy is a promising way. Dasatinib in combination with paclitaxel can potentially be used to overcome triple-negative breast cancer. In this work, we established an liquid chromatography-tandem mass spectrometry method for the simultaneous determination of dasatinib and paclitaxel. T ert -Butyl methyl ether was used to extract paclitaxel, dasatinib, and docetaxel (Internal standard). The study used multiple reaction monitoring mode with electrospray ionization . Monitoring ion pairs for paclitaxel and dasatinib was m/z 876.2→308.2 and m/z 488.3→401.1, respectively. The chromatographic separation was performed on a Hedera ODS-2 column (150 × 2.1 mm, 5 μm; Hanbon Science and Technology, China) maintained at 40°C. The mobile phase was acetonitrile containing 0.3% formic acid (B) and water (A). The gradient elution procedure was used: 0–1 min, 70% B; 1.1–4 min, 90% B; 4.1–7 min, 70% B. The results satisfied the requirements of biological sample determination. The liquid chromatography-tandem mass spectrometry method was successfully applied to the pharmacokinetic study of rats. The rats were simultaneously injected with dasatinib and paclitaxel by tail vein. What is more, this presented method could provide technical support for the clinical combination of these two drugs.

Construction of pH-sensitive targeted micelle system co-delivery with curcumin and dasatinib and evaluation of anti-liver cancer

Xiangle Zeng,Yawen Zhang,Xue Xu,Zhuo Chen,Lanlan Ma,Yushuai Wang,Xuliang Guo,Jianchun Li,Xiu Wang