CRYSTAL GROWTH & DESIGN
·
2015
·
IF 4.891
Jia-Xi Song,Jia-Mei Chen,Tong-Bu Lu
Pharmaceutical cocrystals are an efficient approach to improve the solubility of insoluble active pharmaceutical ingredients (APIs), while the dissolution profiles of pharmaceutical cocrystals usually exhibit a type of “spring and rapid parachute” effect that influences stability and pharmacodynamic sustainability, in which the high apparent solubility induced by the formation of cocrystals can only be maintained for a short time (usually minutes) in the metastable zone and then decreases rapidly afterwords. Herein we reported the preparation and structures of two lenalidomide cocrystals with gallic acid (1, 2). After the formation of cocrystals, the intrinsic dissolution rate and apparent solubility of lenalidomide were found to be enhanced. The high solubility of cocrystals can keep for 48 h without dropping. The result of phase solubility study indicates gallic acid (GA) forms a 1:1 complex with lenalidomide (Rev) in aqueous solution, with a stability constant of 1713.2 L/mol. The multiple hydrogen bonding interactions between GA and Rev are attributed to the formation of GA-Rev complex in aqueous solution and subsequently the constant high solubility of cocrystals.
研究领域:
药学
·
材料科学
✓ 已验证
DOI
高影响因子
CRYSTAL GROWTH & DESIGN
·
2014
·
IF 4.558
Jia-Xi Song,Yan Yan,Jia Yao,Jia-Mei Chen,Tong-Bu Lu
An anticancer drug, lenalidomide, has low oral bioavailability (below 33%) due to its poor solubility in water. To improve its solubility, three cocrystals of lenalidomide with urea (1) and 3,5-dihydroxybenzoic acid (2, 3) were prepared. The structures of 1–3 were determined by single crystal X-ray diffraction, and they all form three-dimensional hydrogen-bonded frameworks between lenalidomide and the coformers. The apparent solubility value and intrinsic dissolution rate of lenalidomide in phosphate buffer of pH 6.8 have been improved after the formation of cocrystals. In addition, 2 and 3 can convert to each other under certain conditions.
研究领域:
药学
·
化学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 23
·期 6
·1-9
·
IF 2.751
Zheng Lv,Shao Yin,Ziguan Cheng,Kekai Wang
Lenalidomide (LEN) has been reported to exert antitumor, anti‑inflammatory, anti‑angiogenic and immunomodulatory activities. However, the effects of LEN in spinal cord injury (SCI) are yet to be fully elucidated. The present study was conducted to identify whether LEN has a healing effect on SCI and to determine the underlying mechanism of action. The viability of H2O2‑stimulated PC12 cells was detected using a Cell Counting Kit‑8 assay. The viability of PC12 cells treated with LEN was examined with an MTT assay. The level of lactate dehydrogenase (LDH) was measured using an LDH assay kit, while the levels of the oxidative stress‑related factors malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase in PC12 cells were determined using commercial kits. Oxidative stress‑related proteins were examined via western blotting. PC12 cell apoptosis was observed using a TUNEL assay, while apoptosis markers and Notch signaling‑related proteins were examined via western blotting. The results of the present study demonstrated that H2O2 decreased PC12 cell viability in a dose‑dependent manner. However, treatment with LEN significantly improved the viability of H2O2‑stimulated PC12 cells and alleviated H2O2‑induced cytotoxic injury. Additionally, LEN treatment inhibited the oxidative stress and apoptosis induced by H2O2 in PC12 cells. Notch signaling‑related protein expression was downregulated after LEN treatment in H2O2‑stimulated PC12 cells. In addition, a Notch agonist reversed the effects of LEN on H2O2‑induced oxidative stress and PC12 cell apoptosis. In summary, it was demonstrated that LEN alleviated the H2O2‑induced injury of PC12 cells by blocking the Notch signaling pathway, suggesting the value of applying LEN to the treatment of SCI.
研究领域:
神经科学
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药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Xiaohe Li,Qing Liang,Shaoyan Gao,Qiuyan Jiang,Fangxia Zhang,Ruiqin Zhang,Hao Ruan,Shuangling Li,Jiaoyan Luan,Ruxia Deng,Honggang Zhou,Hui Huang,Cheng Yang
Idiopathic pulmonary fibrosis (IPF) is a pathological consequence of interstitial pulmonary diseases, and is characterized by the persistence of fibroblasts and excessive deposition of extracellular matrix (ECM). The etiology of IPF is multifactorial. Although the role of inflammation in fibrogenesis is controversial, it is still recognized as an important component and epiphenomenon of IPF. Stimulus increase production of pro-inflammatory cytokines and activation of NF-κB, which will further promote inflammation response and myofibroblast transition. Lenalidomide is an immunomodulatory drug. Previous studies have revealed its anti-tumor effects through regulating immune response. Here we investigate the effect of lenalidomide on post-inflammation fibrosis. In vitro study revealed that lenalidomide inhibited NF-κB signaling in LPS-induced macrophage, and further attenuated macrophage-induced myofibroblast activation. Meanwhile, lenalidomide could inhibit TGF-β1-induced myofibroblast activation through suppressing TGF-β1 downstream MAPK signaling. In vivo study showed that lenalidomide inhibited pro-inflammatory cytokines TNF-α and IL-6 while enhanced anti-fibrotic cytokines IFN-γ and IL-10 in bleomycin-induced inflammation model, and attenuated pulmonary fibrosis and collagen deposition in the following fibrosis stage. In conclusion, our results demonstrate that lenalidomide possesses potential anti-fibrotic effects through suppressing NF-κB signaling.
研究领域:
药理学
·
肺科学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yulu Yang,Rui Chen,Yi Gong,Weihu Yang,Ke Li,Wuzhe Fan,Shuangquan Gou,Pengfei Gao,Tingting He,Kaiyong Cai
Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells . Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo . RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment . Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.
研究领域:
肿瘤学
·
血液学
·
纳米技术
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免疫治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Yue-Yue Chang,Hai-Long Wu,Huan Fang,Tong Wang,Yang-Zi Ouyang,Xiao-Dong Sun,Gao-Yan Tong,Yu-Jie Ding,Ru-Qin Yu
Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis , satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%–116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%–114.8% and 84.5%–106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.
研究领域:
分析化学
·
药物分析
·
化学计量学
✓ 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）