Gelated Vorinostat with inner-lysosome triggered release for tumor-targeting chemotherapy

Guo, Changyong; Wang, Qirong; Zhang, Xing-Jie; Lu, Fengkun; Sun, Miao; Zeng, Peiyu; She, Lan; Wang, Bingkai; Zhang, Yunchang; Wang, Chen; Ma, Zhiqiang; Yang, Feng

doi:10.1016/j.colsurfb.2020.111144

Cited by 4 publications

(2 citation statements)

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“…17 However, the solubility of PXD101 in water is only 0.14 mg/ mL (25 °C); according to the BCS classification, it is classified as a biopharmaceutical classification system II (BCSII) drug, that is, it has low solubility and high permeability. 21 PXD101 lyophilized powder is mainly used for intravenous injection, and the US Food and Drug Administration-approved commercial specifications for the drug is 500 mg. In order to maintain the drug concentration in the body, the freeze-dried powder injection will produce adverse reactions such as nausea, vomiting, fatigue, fever, anemia, etc., and even lead to serious side effects such as liver failure, thrombocytopenia, increased creatinine, gastrointestinal toxicity, pneumonia, or tumor lysis syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…As a histone deacetylase inhibitor, belinostat (PXD101, Figure ) was approved for treating refractory T-cell lymphoma and is currently administered intravenously. , Due to the unique hydroxamic acid functional group in the molecular structure, PXD101 also plays a crucial part in the treatment of cancer, cardiovascular disease, HIV, Alzheimer’s disease, malaria, and other diseases, especially in combination with other anticancer drugs and or radiation therapy. − However, the solubility of PXD101 in water is only 0.14 mg/mL (25 °C); according to the BCS classification, it is classified as a biopharmaceutical classification system II (BCSII) drug, that is, it has low solubility and high permeability . PXD101 lyophilized powder is mainly used for intravenous injection, and the US Food and Drug Administration-approved commercial specifications for the drug is 500 mg.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Solubility Enhancement of Anticancer Drug Belinostat via the Co-crystallization Strategy: Synthesis, Characterization, and Antitumor Activity In Vitro Evaluation

Ouyang

Cao

et al. 2022

Crystal Growth & Design

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Belinostat (PXD101), a biopharmaceutical classification system II (BCSII) drug approved for treating refractory T-cell lymphoma, is currently administered by intravenous injection. To improve patient compliance, the development of oral formulations of PXD101 has attracted attention. Because the solubility and dissolution rate of active pharmaceutical ingredients can affect the therapeutic effect of the oral formulations, this work explores solid-state form modification of PXD101 by co-crystallization with four coformers, namely, theophylline, isonicotinamide (INA), isoniazid (INH), and l-proline (l-Pro) to solve the problem of poor water solubility. The four cocrystals were obtained on the basis of N–H···O, O–H···O, and O–H···N synthons. All the four obtained multicomponent crystals were characterized by powder X-ray diffraction (PXRD) and thermal analysis, meanwhile, crystal structure determination was performed by single-crystal XRD. The results of CrystalCMP show the similar packing patterns of PXD101-INA and PXD101-INH cocrystals. The data analysis from powder dissolution experiments suggested that the apparent solubility of the obtained multicomponent crystals is 1.14–2.22 times more than that of PXD101, and PXD101-l-Pro shows a completely different dissolution behavior from that of the other three cocrystals. Finally, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay experiments demonstrated that the PXD101-INA cocrystal can significantly inhibit the proliferation of Michigan Cancer Foundation-7 (MCF-7) cells even at a low concentration (0.01 μM). Such results shed light on the potential value of multicomponent crystals in the further development of pharmaceutical products.

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Section: Introductionmentioning

confidence: 99%