Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis
Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006423002077 |
| _version_ | 1797682475538841600 |
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| author | Zhong-Hua Chen De-Yan Du Yi-Fei Fu Jun-Jie Wu Dan-Yang Guo Yue-Yue Li Meng-Nan Chen Zheng-Dong Yuan Kai-Wen Zhang Zhen-Yu Zhang Xia Li Feng-Lai Yuan |
| author_facet | Zhong-Hua Chen De-Yan Du Yi-Fei Fu Jun-Jie Wu Dan-Yang Guo Yue-Yue Li Meng-Nan Chen Zheng-Dong Yuan Kai-Wen Zhang Zhen-Yu Zhang Xia Li Feng-Lai Yuan |
| author_sort | Zhong-Hua Chen |
| collection | DOAJ |
| description | Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)–poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP. |
| first_indexed | 2024-03-12T00:01:15Z |
| format | Article |
| id | doaj.art-920af887a1dc4aaa8803f480b8a6b734 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-03-12T00:01:15Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-920af887a1dc4aaa8803f480b8a6b7342023-09-18T04:30:15ZengElsevierMaterials Today Bio2590-00642023-10-0122100747Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosisZhong-Hua Chen0De-Yan Du1Yi-Fei Fu2Jun-Jie Wu3Dan-Yang Guo4Yue-Yue Li5Meng-Nan Chen6Zheng-Dong Yuan7Kai-Wen Zhang8Zhen-Yu Zhang9Xia Li10Feng-Lai Yuan11Affiliated Hospital 3 of Nantong University, Medical School of Nantong University, Jiangsu, ChinaSchool of Chemical and Material Engineering, Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, ChinaInstitute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, China; Corresponding author.Affiliated Hospital 3 of Nantong University, Medical School of Nantong University, Jiangsu, China; Institute of Integrated Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Jiangsu, China; Corresponding author. Affiliated Hospital 3 of Nantong University, Medical school of Nantong University, Jiangsu, China.Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)–poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP.http://www.sciencedirect.com/science/article/pii/S2590006423002077Postmenopausal osteoporosisCitric acidBone-targetedpH-sensitiveSide effects |
| spellingShingle | Zhong-Hua Chen De-Yan Du Yi-Fei Fu Jun-Jie Wu Dan-Yang Guo Yue-Yue Li Meng-Nan Chen Zheng-Dong Yuan Kai-Wen Zhang Zhen-Yu Zhang Xia Li Feng-Lai Yuan Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis Materials Today Bio Postmenopausal osteoporosis Citric acid Bone-targeted pH-sensitive Side effects |
| title | Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| title_full | Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| title_fullStr | Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| title_full_unstemmed | Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| title_short | Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| title_sort | citric acid modified ph sensitive bone targeted delivery of estrogen for the treatment of postmenopausal osteoporosis |
| topic | Postmenopausal osteoporosis Citric acid Bone-targeted pH-sensitive Side effects |
| url | http://www.sciencedirect.com/science/article/pii/S2590006423002077 |
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