Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice
Li Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-10-01
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| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/enhanced-antitumor-efficacy-of-poly-dl-lactide-co-glycolide-based-meth-peer-reviewed-article-DDDT |
| _version_ | 1811324473733808128 |
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| author | Gao L Xia L Zhang R Duan D Liu X Xu J Luo L |
| author_facet | Gao L Xia L Zhang R Duan D Liu X Xu J Luo L |
| author_sort | Gao L |
| collection | DOAJ |
| description | Li Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of Pharmaceutical Research, Anhui Zhongren Science and Technology Co., Ltd., Hefei, People’s Republic of China Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. Results: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity. Conclusion: These results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer. Keywords: methotrexate, implant, sustained release, poly(D,L-lactide-co-glycolide), intratumoral chemotherapy |
| first_indexed | 2024-04-13T14:16:03Z |
| format | Article |
| id | doaj.art-0da528fe97ce4933831e478775c72f30 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-13T14:16:03Z |
| publishDate | 2017-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-0da528fe97ce4933831e478775c72f302022-12-22T02:43:39ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-10-01Volume 113065307535277Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing miceGao LXia LZhang RDuan DLiu XXu JLuo LLi Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of Pharmaceutical Research, Anhui Zhongren Science and Technology Co., Ltd., Hefei, People’s Republic of China Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. Results: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity. Conclusion: These results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer. Keywords: methotrexate, implant, sustained release, poly(D,L-lactide-co-glycolide), intratumoral chemotherapyhttps://www.dovepress.com/enhanced-antitumor-efficacy-of-poly-dl-lactide-co-glycolide-based-meth-peer-reviewed-article-DDDTmethotrexateimplantsustained releasepoly (DL-lactide-co-glycolide)intratumoral chemotherapy |
| spellingShingle | Gao L Xia L Zhang R Duan D Liu X Xu J Luo L Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice Drug Design, Development and Therapy methotrexate implant sustained release poly (D L-lactide-co-glycolide) intratumoral chemotherapy |
| title | Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice |
| title_full | Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice |
| title_fullStr | Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice |
| title_full_unstemmed | Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice |
| title_short | Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice |
| title_sort | enhanced antitumor efficacy of poly d l lactide co glycolide based methotrexate loaded implants on sarcoma 180 tumor bearing mice |
| topic | methotrexate implant sustained release poly (D L-lactide-co-glycolide) intratumoral chemotherapy |
| url | https://www.dovepress.com/enhanced-antitumor-efficacy-of-poly-dl-lactide-co-glycolide-based-meth-peer-reviewed-article-DDDT |
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