Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System
<b>Background:</b> CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effe...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Journal of Functional Biomaterials |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-4983/15/12/372 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850041807090483200 |
|---|---|
| author | Hui Li Junwei Liu Jingru Wang Zhuoyue Li Jianming Yu Xu Huang Bingchuan Wan Xiangbao Meng Xuan Zhang |
| author_facet | Hui Li Junwei Liu Jingru Wang Zhuoyue Li Jianming Yu Xu Huang Bingchuan Wan Xiangbao Meng Xuan Zhang |
| author_sort | Hui Li |
| collection | DOAJ |
| description | <b>Background:</b> CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol)<sub>2000</sub> (DSPE-PEG<sub>2000</sub>) to improve the anti-tumor effect of CY1-4. <b>Methods</b>: The solubility and dissolution of MSNM@CY1-4 were investigated, and its bioavailability, anti-tumor efficacy, IDO inhibitory ability and immune mechanism were evaluated in vivo. <b>Results</b>: CY1-4 was loaded in MSNM@CY1-4 in an amorphous form, and MSNM@CY1-4 could significantly improve the solubility (up to about 200 times) and dissolution rate of CY1-4. In vivo studies showed that the oral bioavailability of CY1-4 in 20 mg/kg MSNM@CY1-4 was about 23.9-fold more than that in 50 mg/kg CY1-4 suspension. In B16F10 tumor-bearing mice, MSNM@CY1-4 significantly inhibited tumor growth, prolonged survival time, significantly inhibited IDO activity in blood and tumor tissues, and reduced Tregs in tumor tissues and tumor-draining lymph nodes to improve anti-tumor efficacy. <b>Conclusions</b>: The nano-skeleton drug delivery system (MSNM@CY1-4) constructed in this study is a potential drug delivery platform for improving the anti-tumor effect of oral poorly water-soluble CY1-4. |
| format | Article |
| id | doaj-art-84df10c2096540669c1665cc76af015e |
| institution | DOAJ |
| issn | 2079-4983 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj-art-84df10c2096540669c1665cc76af015e2025-08-20T02:55:41ZengMDPI AGJournal of Functional Biomaterials2079-49832024-12-01151237210.3390/jfb15120372Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery SystemHui Li0Junwei Liu1Jingru Wang2Zhuoyue Li3Jianming Yu4Xu Huang5Bingchuan Wan6Xiangbao Meng7Xuan Zhang8Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China<b>Background:</b> CY1-4, 9-nitropyridine [2′,3′:4,5] pyrimido [1,2-α] indole -5,11- dione, is an indoleamine 2,3-dioxygenase (IDO) inhibitor and a poorly water-soluble substance. It is very important to increase the solubility of CY1-4 to improve its bioavailability and therapeutic effect. In this study, the mesoporous silica nano-skeleton carrier material Sylysia was selected as the carrier to load CY1-4, and then the CY1-4 nano-skeleton drug delivery system (MSNM@CY1-4) was prepared by coating the hydrophilic polymer material Hydroxypropyl methylcellulose (HPMC) and the lipid material Distearoylphosphatidyl-ethanolamine-poly(ethylene glycol)<sub>2000</sub> (DSPE-PEG<sub>2000</sub>) to improve the anti-tumor effect of CY1-4. <b>Methods</b>: The solubility and dissolution of MSNM@CY1-4 were investigated, and its bioavailability, anti-tumor efficacy, IDO inhibitory ability and immune mechanism were evaluated in vivo. <b>Results</b>: CY1-4 was loaded in MSNM@CY1-4 in an amorphous form, and MSNM@CY1-4 could significantly improve the solubility (up to about 200 times) and dissolution rate of CY1-4. In vivo studies showed that the oral bioavailability of CY1-4 in 20 mg/kg MSNM@CY1-4 was about 23.9-fold more than that in 50 mg/kg CY1-4 suspension. In B16F10 tumor-bearing mice, MSNM@CY1-4 significantly inhibited tumor growth, prolonged survival time, significantly inhibited IDO activity in blood and tumor tissues, and reduced Tregs in tumor tissues and tumor-draining lymph nodes to improve anti-tumor efficacy. <b>Conclusions</b>: The nano-skeleton drug delivery system (MSNM@CY1-4) constructed in this study is a potential drug delivery platform for improving the anti-tumor effect of oral poorly water-soluble CY1-4.https://www.mdpi.com/2079-4983/15/12/372MSNM@CY1-4indoleamine 2,3-dioxygenasenano-skeletonanti-tumoranti-tumor immune |
| spellingShingle | Hui Li Junwei Liu Jingru Wang Zhuoyue Li Jianming Yu Xu Huang Bingchuan Wan Xiangbao Meng Xuan Zhang Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System Journal of Functional Biomaterials MSNM@CY1-4 indoleamine 2,3-dioxygenase nano-skeleton anti-tumor anti-tumor immune |
| title | Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System |
| title_full | Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System |
| title_fullStr | Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System |
| title_full_unstemmed | Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System |
| title_short | Improving the Anti-Tumor Effect of Indoleamine 2,3-Dioxygenase Inhibitor CY1-4 by CY1-4 Nano-Skeleton Drug Delivery System |
| title_sort | improving the anti tumor effect of indoleamine 2 3 dioxygenase inhibitor cy1 4 by cy1 4 nano skeleton drug delivery system |
| topic | MSNM@CY1-4 indoleamine 2,3-dioxygenase nano-skeleton anti-tumor anti-tumor immune |
| url | https://www.mdpi.com/2079-4983/15/12/372 |
| work_keys_str_mv | AT huili improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT junweiliu improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT jingruwang improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT zhuoyueli improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT jianmingyu improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT xuhuang improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT bingchuanwan improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT xiangbaomeng improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem AT xuanzhang improvingtheantitumoreffectofindoleamine23dioxygenaseinhibitorcy14bycy14nanoskeletondrugdeliverysystem |