pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy
Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087623000594 |
| _version_ | 1797689520243605504 |
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| author | Xin Liu Zhexiang Wang Xiaodie Ren Xinyang Chen Jinjin Tao Yuanhui Guan Xuefeng Yang Rupei Tang Guoqing Yan |
| author_facet | Xin Liu Zhexiang Wang Xiaodie Ren Xinyang Chen Jinjin Tao Yuanhui Guan Xuefeng Yang Rupei Tang Guoqing Yan |
| author_sort | Xin Liu |
| collection | DOAJ |
| description | Currently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.16%), electric neutrality, strong hydrophobicity, and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH. These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation. |
| first_indexed | 2024-03-12T01:47:44Z |
| format | Article |
| id | doaj.art-bd9a4553b4464ca781e06e45d4e246ba |
| institution | Directory Open Access Journal |
| issn | 1818-0876 |
| language | English |
| last_indexed | 2024-03-12T01:47:44Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj.art-bd9a4553b4464ca781e06e45d4e246ba2023-09-09T04:54:54ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762023-07-01184100832pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapyXin Liu0Zhexiang Wang1Xiaodie Ren2Xinyang Chen3Jinjin Tao4Yuanhui Guan5Xuefeng Yang6Rupei Tang7Guoqing Yan8Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaEngineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaCorresponding authors.; Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaCorresponding authors.; Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, Hefei 230601, ChinaCurrently, the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy, owing to its precise structure, high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract, blood circulation and tumor tissues compared to other oral nanomedicines. Herein, this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes, which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters. The precise nano-prodrugs exhibit extraordinarily high drug loading (68.16%), electric neutrality, strong hydrophobicity, and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH. These favorable physicochemical properties can effectively facilitate gastrointestinal absorption, blood circulation stability, tumor accumulation, cellular uptake, and cytotoxicity, therefore achieving high oral relative bioavailability (358.72%) and significant tumor growth inhibition while decreasing side effects. Thus, this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.http://www.sciencedirect.com/science/article/pii/S1818087623000594Nano-prodrugspH sensitivitySize transitionOral chemotherapy |
| spellingShingle | Xin Liu Zhexiang Wang Xiaodie Ren Xinyang Chen Jinjin Tao Yuanhui Guan Xuefeng Yang Rupei Tang Guoqing Yan pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy Asian Journal of Pharmaceutical Sciences Nano-prodrugs pH sensitivity Size transition Oral chemotherapy |
| title | pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy |
| title_full | pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy |
| title_fullStr | pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy |
| title_full_unstemmed | pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy |
| title_short | pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy |
| title_sort | ph triggered dynamic erosive small molecule chlorambucil nano prodrugs mediate robust oral chemotherapy |
| topic | Nano-prodrugs pH sensitivity Size transition Oral chemotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1818087623000594 |
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