NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel
文献类型：期刊论文
| 作者 | Xu, Jian1,2; Ren, Xiaohong1; Guo, Tao1; Sun, Xian1,2; Chen, Xiaojin1; Patterson, Laurence H.3; Li, Haiyan1 ; Zhang, Jiwen1,2
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| 刊名 | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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| 出版日期 | 2019-10-01 |
| 卷号 | 138页码:8 |
| 关键词 | Cyclodextrins NLG919 Solubility enhancement Paclitaxel IDO-1 combination immunochemotherapy |
| ISSN号 | 0928-0987 |
| DOI | 10.1016/j.ejps.2019.105034 |
| 通讯作者 | Li, Haiyan(lihaiyan821005@163.com) ; Zhang, Jiwen(jwzhang@simm.ac.cn) |
| 英文摘要 | NLG919 is an effective small molecule inhibitor of indoleamine 2, 3-dioxygenase-1 (IDO-1) in anti-tumour immunotherapy, but the poor aqueous solubility limits its application for effective intravenous dosing. In this study a cyclodextrin (CD) complexation strategy has been systematically evaluated to achieve a simple and feasible method to prepare an NLG919 injectable formulation. From a series of CDs, HP-beta-CD proved to be the most conducive for NLG919 solubilization (approx 800-fold increase). Characterization studies using DSC, H-1 NMR, XRPD and molecular simulation demonstrated that the NLG919/HP-beta-CD loading mechanism involved an increasing pH-dependent binding affinity. Importantly cell-based studies in vitro and anti-tumour activity in vivo demonstrated that the pharmacological activity of NLG919 as an IDO-1 inhibitor was not influenced by HP-beta-CD complexation. Furthermore, the combination of NLG919/HP-beta-CD with paclitaxel (PTX) significantly improved anti-tumour chemotherapy compared to PTX alone. In summary, NLG919/HP-beta-CD is shown to highly enhance the aqueous solubility of NLG919 with activity unaffected, greatly facilitating the intravenous use of this small molecule immunotherapeutic to improve the efficacy of PTX. |
| WOS关键词 | INDOLEAMINE 2,3-DIOXYGENASE ; TRYPTOPHAN DEGRADATION ; INHIBITOR NLG919 ; DENDRITIC CELLS ; CANCER ; DELIVERY ; CYCLODEXTRINS ; IDO ; DOXORUBICIN ; TOLERANCE |
| 资助项目 | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050307] ; Research Foundation of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences[CASIMM0120182001] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000485819800017 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/288764]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Haiyan; Zhang, Jiwen |
| 作者单位 | 1.Chinese Acad Sci, Ctr Drug Delivery Syst, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Univ Bradford, Fac Life Sci, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England |
| 推荐引用方式 GB/T 7714 | Xu, Jian,Ren, Xiaohong,Guo, Tao,et al. NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel[J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,2019,138:8. |
| APA | Xu, Jian.,Ren, Xiaohong.,Guo, Tao.,Sun, Xian.,Chen, Xiaojin.,...&Zhang, Jiwen.(2019).NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel.EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES,138,8. |
| MLA | Xu, Jian,et al."NLG919/cyclodextrin complexation and anti-cancer therapeutic benefit as a potential immunotherapy in combination with paclitaxel".EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 138(2019):8. |
入库方式： OAI收割
来源：上海药物研究所
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