Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery
The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosoma...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-12-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/9/12/698 |
| _version_ | 1811268095650562048 |
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| author | Yinglei Zhai Xing Zhou Lina Jia Chao Ma Ronghua Song Yanhao Deng Xueyao Hu Wei Sun |
| author_facet | Yinglei Zhai Xing Zhou Lina Jia Chao Ma Ronghua Song Yanhao Deng Xueyao Hu Wei Sun |
| author_sort | Yinglei Zhai |
| collection | DOAJ |
| description | The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX) prodrug micelles based on functionalized poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) diblock polymer with an acid-cleavable acetal (Ace) linkage (mPEG-PCL-Ace-PTX). The mPEG-PCL-Ace-PTX5 with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM) into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX5 micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX5 micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT) assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy. |
| first_indexed | 2024-04-12T21:14:38Z |
| format | Article |
| id | doaj.art-141b058fbae74b64896176db3e1b242a |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-04-12T21:14:38Z |
| publishDate | 2017-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-141b058fbae74b64896176db3e1b242a2022-12-22T03:16:28ZengMDPI AGPolymers2073-43602017-12-0191269810.3390/polym9120698polym9120698Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug DeliveryYinglei Zhai0Xing Zhou1Lina Jia2Chao Ma3Ronghua Song4Yanhao Deng5Xueyao Hu6Wei Sun7Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaHainan Institute of Materia Medica, Haikou 570311, ChinaDepartment of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, ChinaCollege of Food & Pharmaceutical Engineering, Guizhou Institute of Technology, Guizhou 550003, ChinaDepartment of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, ChinaThe differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX) prodrug micelles based on functionalized poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) diblock polymer with an acid-cleavable acetal (Ace) linkage (mPEG-PCL-Ace-PTX). The mPEG-PCL-Ace-PTX5 with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM) into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX5 micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX5 micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT) assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy.https://www.mdpi.com/2073-4360/9/12/698prodrugpolymer micellespH-sensitiveacetalpaclitaxel |
| spellingShingle | Yinglei Zhai Xing Zhou Lina Jia Chao Ma Ronghua Song Yanhao Deng Xueyao Hu Wei Sun Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery Polymers prodrug polymer micelles pH-sensitive acetal paclitaxel |
| title | Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery |
| title_full | Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery |
| title_fullStr | Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery |
| title_full_unstemmed | Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery |
| title_short | Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery |
| title_sort | acetal linked paclitaxel polymeric prodrug based on functionalized mpeg pcl diblock polymer for ph triggered drug delivery |
| topic | prodrug polymer micelles pH-sensitive acetal paclitaxel |
| url | https://www.mdpi.com/2073-4360/9/12/698 |
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