Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system
Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, th...
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Elsevier
2024-12-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424003405 |
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| author | Guangyong Lin Huirong Huang Meng Sun Zhinan He Shengjie Li Xindan Liang Yuqi Yan Chenyu Qiu Shize Li Xinyu Zhao Wanling Zhu Longfa Kou Ruijie Chen |
| author_facet | Guangyong Lin Huirong Huang Meng Sun Zhinan He Shengjie Li Xindan Liang Yuqi Yan Chenyu Qiu Shize Li Xinyu Zhao Wanling Zhu Longfa Kou Ruijie Chen |
| author_sort | Guangyong Lin |
| collection | DOAJ |
| description | Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a ''two-stage'' drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment. |
| format | Article |
| id | doaj-art-075b75e268e34d95bd8d046822a24911 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-075b75e268e34d95bd8d046822a249112025-08-20T01:55:30ZengElsevierMaterials Today Bio2590-00642024-12-012910127910.1016/j.mtbio.2024.101279Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery systemGuangyong Lin0Huirong Huang1Meng Sun2Zhinan He3Shengjie Li4Xindan Liang5Yuqi Yan6Chenyu Qiu7Shize Li8Xinyu Zhao9Wanling Zhu10Longfa Kou11Ruijie Chen12Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, ChinaWenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China; Corresponding author. Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, 325027, China; Corresponding author. Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China.Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a ''two-stage'' drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.http://www.sciencedirect.com/science/article/pii/S2590006424003405Two-stage nanoparticleOsteoarthritisRapamycinAutophagyChondrocyte |
| spellingShingle | Guangyong Lin Huirong Huang Meng Sun Zhinan He Shengjie Li Xindan Liang Yuqi Yan Chenyu Qiu Shize Li Xinyu Zhao Wanling Zhu Longfa Kou Ruijie Chen Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system Materials Today Bio Two-stage nanoparticle Osteoarthritis Rapamycin Autophagy Chondrocyte |
| title | Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system |
| title_full | Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system |
| title_fullStr | Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system |
| title_full_unstemmed | Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system |
| title_short | Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system |
| title_sort | enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two stage drug delivery system |
| topic | Two-stage nanoparticle Osteoarthritis Rapamycin Autophagy Chondrocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424003405 |
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