Pharmaceutics
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2022
·Vol. 14
·期 1
·197
·
IF 6.525
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
研究领域:
药学
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Fundamental Research
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2024
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IF 5.7
Rong Li,Yaohua Wei,Changhao Xiong,Jingwei Wang,Yixuan Lin,Ronghui Deng,Hao Qin,Yang Chen,Nan Li,Guyu Zheng,Yuanyuan Lv,Jian Shi,Tingting Yu,Yiye Li,Jing Wang,Ruifang Zhao,Changsheng Liu,Guangjun Nie
The senescence of bone marrow-derived mesenchymal stem cells is involved in osteoporosis. The combination of dasatinib and quercetin has been explored to alleviate bone loss by efficiently reducing senescent cell populations. However, senolytic therapy by dasatinib and quercetin requires a precise ratio for better therapeutic effects, which is hard to achieve by oral administration. Meanwhile, the poor water solubility of these compounds limits their bioavailability, and their non-specific action could hamper effective penetration and targeting within relevant tissues. Herein, we developed alendronate-functionalized liposomes carrying dasatinib and quercetin (Aln-Lipo-DQ), focusing mainly on senescence-associated osteoporosis induced by chemotherapy or radiotherapy. Alendronate helps liposomes deliver dasatinib and quercetin to the femur and tibias, effectively removing senescent cells from bone tissue and increasing bone volume fraction from 5.05% to 11.95% in the chemotherapy-induced osteoporosis mouse model. We also found a 2.91-fold increase in bone volume fraction in Aln-Lipo-DQ treated groups compared to the control in radiotherapy models. This selectively targeting bone and reducing senescent cells holds great promise for cancer treatment-related and senescence-associated bone disorders.
研究领域:
医学
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药理学
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生物技术
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
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.
研究领域:
药理学
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眼科
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Separation Science Plus
·
2023
·Vol. 6
·期 8
·2300055
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IF 1.1
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.
研究领域:
药物分析
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肿瘤学
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临床药理学
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产品关联
DOI
高影响因子
Journal of the Taiwan Institute of Chemical Engineers
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2024
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IF 5.5
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.
研究领域:
药学
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纳米技术
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制药工程
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产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
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2024
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IF 4.9
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.
研究领域:
分析化学
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药物分析
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生物医学工程
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DOI
高影响因子
Analytical Methods
·
2018
·Vol. 11
·期 4
·443-453
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IF 2.073
Pramod K. Kalambate,Yankai Li,Yue Shen,Yunhui Huang
In this work, a novel highly sensitive electrochemical sensing platform has been developed for simultaneous determination of anticancer drugs doxorubicin (DOX) and dasatinib (DAS) by means of mesoporous Pd@Pt core–shell nanoparticles supported on MWCNT (Pd@Pt/MWCNT). The electrochemical behaviour of the drugs was assessed through cyclic voltammetry, while simultaneous determination was carried out using adsorptive stripping square wave voltammetry (AdSSWV). Under optimized conditions, the method exhibits linear responses towards simultaneous determination of DOX and DAS in the concentration ranges of 4.4–8580 nM and 38–9880 nM, with detection limits of 0.86 and 6.72 nM, respectively. Furthermore, the proposed platform was successfully used for reliable determination of DOX and DAS in urine and blood serum samples with good accuracy and precision. The satisfactory recoveries obtained in blood serum and urine samples showed the potential for application of the proposed platform in quality control in the pharmaceutical industry, clinical analysis and optimization of chemotherapeutic treatment. We found that the established sensor has several advantages in terms of high sensitivity and selectivity, ease of preparation, short analysis time, long-term stability and fast response.
研究领域:
分析化学
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药物分析
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癌症治疗
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Analysis
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2017
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IF 0
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).
研究领域:
药理学
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临床医学
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分析化学
✓ 已验证
DOI
Biomaterials Science
·
2021
·Vol. 9
·期 7
·2571-2583
·
IF 6.843
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.
研究领域:
药理学
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眼科学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
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.
研究领域:
癌症研究
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药学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-13
·
IF 17.694
Sun Jie,Wang Ming,Zhong Yaqi,Ma Xuan,Sun Shimin,Xu Chenzhong,Peng Linyuan,Li Guo,Zhang Liting,Liu Zuojun,Ai Ding,Liu Baohua
The progressive decline of physiological function and the increased risk of age-related diseases challenge healthy aging. Multiple anti-aging manipulations, such as senolytics, have proven beneficial for health; however, the biomarkers that label in vivo senescence at systemic levels are lacking, thus hindering anti-aging applications. In this study, we generate a Glb1 +/m ‒Glb1-2A-mCherry (GAC) reporter allele at the Glb1 gene locus, which encodes lysosomal β-galactosidase—an enzyme elevated in tissues of old mice. A linear correlation between GAC signal and chronological age is established in a cohort of middle-aged (9 to 13 months) Glb1 +/m mice. The high GAC signal is closely associated with cardiac hypertrophy and a shortened lifespan. Moreover, the GAC signal is exponentially increased in pathological senescence induced by bleomycin in the lung. Senolytic dasatinib and quercetin (D + Q) reduce GAC signal in bleomycin treated mice. Thus, the Glb1-2A-mCherry reporter mice monitors systemic aging and function decline, predicts lifespan, and may facilitate the understanding of aging mechanisms and help in the development of anti-aging interventions.
研究领域:
衰老
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分子生物学
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遗传学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Xiangle Zeng,Hairong Wang,Yawen Zhang,Xue Xu,Xinyi Yuan,Jianchun Li
Purpose This study emphasized that dasatinib (DAS) and olaparib (OLA) have synergistic effects on triple negative breast cancer, by inducing DNA damage and inhibiting DNA damage repair. However, poor water solubility, short half-life of drugs, and low drug concentration in tumor tissue limit the clinical application.Methods In this research, acid-sensitive ester bonds were used to connect hydrophobic DAS and hydrophilic hyaluronic acid (HA) to form the amphiphilic polymer prodrug HA-DAS, and then OLA was added as the core, the HA-DAS was used as the carrier to form nanomicelles (HDO-NPs) in aqueous. The characterization and drug release of HDO-NPs were studied, and the cytotoxicity, targeting effect, and intracellular transport behavior of HDO-NPs were evaluated in MDA-MB-231. In addition, the pharmacokinetic and therapeutic effect of HDO-NPs were further verified in vivo.Results In vitro characterizations showed that HDO-NPs were spherical with uniform particle size, good stability and anti-dilution ability, and displayed favorable pH-responsive drug release behavior. In addition, the cell experiments showed that HDO-NPs could be effectively taken up by binding to the overexpressed CD44 proteins of MDA-MB-231 cells, resulting in increased intracellular drug concentration. In vivo experiments showed that HDO-NPs can effectively target tumor tissues, have excellent therapeutic effects on tumor, significantly prolong the circulation time of drugs in vivo, and effectively improved the bioavailability of drugs.Conclusion DAS and OLA were designed into micelles, the efficacy of HDO-NPs was higher than that of free drugs. Therefore, HDO-NPs have good application prospects in the treatment of triple negative breast cancer.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）