Drug retention after intradiscal administration
Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics. Release...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2024.2415579 |
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| author | Imke Rudnik-Jansen Jie Du Nina Karssemakers-Degen Anna R. Tellegen Parvesh Wadhwani Daniele Zuncheddu Björn P. Meij Jens Thies Pieter Emans Fetullah C. Öner George Mihov Joao Pedro Garcia Anne S. Ulrich Sibylle Grad Marianna A. Tryfonidou Hugo van Ingen Laura B. Creemers |
| author_facet | Imke Rudnik-Jansen Jie Du Nina Karssemakers-Degen Anna R. Tellegen Parvesh Wadhwani Daniele Zuncheddu Björn P. Meij Jens Thies Pieter Emans Fetullah C. Öner George Mihov Joao Pedro Garcia Anne S. Ulrich Sibylle Grad Marianna A. Tryfonidou Hugo van Ingen Laura B. Creemers |
| author_sort | Imke Rudnik-Jansen |
| collection | DOAJ |
| description | Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics. Release and retention of an inactive hydrophilic fluorine-19 labeled peptide (19F-P) as model for regenerative peptides was studied in a whole IVD culture model by measuring the 19F-NMR (nuclear magnetic resonance) signal in culture media and IVD tissue extracts. In another set-up, noninvasive near-infrared imaging was used to visualize IR-780, as hydrophobic small molecular drug model, retention upon injection into healthy and degenerative caudal IVDs in a rat model of disk degeneration. Furthermore, IR-780-loaded degradable polyester amide microspheres (PEAM) were injected into healthy and needle pricked degenerative IVDs, subcutaneously, and in knee joints with and without surgically-induced osteoarthritis (OA). Most 19F-P was released from the IVD after 7 days. IR-780 signal intensity declined over a 14-week period after bolus injection, without a difference between healthy and degenerative disks. IR-780 signal declined faster in the skin and knee joints compared to the IVDs. IR-780 delivery by PEAMs enhanced disk retention beyond 16 weeks. Moreover, in degenerated IVDs the IR-780 signal was higher over time than in healthy IVDs while no difference between OA and healthy joints was noted. We conclude that the clearance of peptides and hydrophobic small molecules from the IVD is relatively fast. These results illustrate that development of controlled release formulations should take into account the target anatomical location and local (patho)biology. |
| format | Article |
| id | doaj-art-e74ff26b3ae344bf99b69a5fc7b3d7c3 |
| institution | OA Journals |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-e74ff26b3ae344bf99b69a5fc7b3d7c32025-08-20T02:30:28ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642024-12-0131110.1080/10717544.2024.2415579Drug retention after intradiscal administrationImke Rudnik-Jansen0Jie Du1Nina Karssemakers-Degen2Anna R. Tellegen3Parvesh Wadhwani4Daniele Zuncheddu5Björn P. Meij6Jens Thies7Pieter Emans8Fetullah C. Öner9George Mihov10Joao Pedro Garcia11Anne S. Ulrich12Sibylle Grad13Marianna A. Tryfonidou14Hugo van Ingen15Laura B. Creemers16Department of Orthopedics, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, Utrecht, The NetherlandsDSM Biomedical, Geleen, The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsInstitute of Biological Interfaces (IBG2) and Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Karlsruhe, GermanyAO Research Institute Davos, Davos, SwitzerlandDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsDSM Biomedical, Geleen, The NetherlandsDepartment of Orthopaedics, Maastricht University Medical Center, Joint-Preserving Clinic Maastricht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, Utrecht, The NetherlandsDSM Biomedical, Geleen, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, Utrecht, The NetherlandsInstitute of Biological Interfaces (IBG2) and Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Karlsruhe, GermanyAO Research Institute Davos, Davos, SwitzerlandDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The NetherlandsNMR Group, Bijvoet Centre for Biomolecular Research, Utrecht University, Utrecht, The NetherlandsDepartment of Orthopedics, University Medical Center Utrecht, Utrecht, The NetherlandsIntradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics. Release and retention of an inactive hydrophilic fluorine-19 labeled peptide (19F-P) as model for regenerative peptides was studied in a whole IVD culture model by measuring the 19F-NMR (nuclear magnetic resonance) signal in culture media and IVD tissue extracts. In another set-up, noninvasive near-infrared imaging was used to visualize IR-780, as hydrophobic small molecular drug model, retention upon injection into healthy and degenerative caudal IVDs in a rat model of disk degeneration. Furthermore, IR-780-loaded degradable polyester amide microspheres (PEAM) were injected into healthy and needle pricked degenerative IVDs, subcutaneously, and in knee joints with and without surgically-induced osteoarthritis (OA). Most 19F-P was released from the IVD after 7 days. IR-780 signal intensity declined over a 14-week period after bolus injection, without a difference between healthy and degenerative disks. IR-780 signal declined faster in the skin and knee joints compared to the IVDs. IR-780 delivery by PEAMs enhanced disk retention beyond 16 weeks. Moreover, in degenerated IVDs the IR-780 signal was higher over time than in healthy IVDs while no difference between OA and healthy joints was noted. We conclude that the clearance of peptides and hydrophobic small molecules from the IVD is relatively fast. These results illustrate that development of controlled release formulations should take into account the target anatomical location and local (patho)biology.https://www.tandfonline.com/doi/10.1080/10717544.2024.2415579Drug retentionpeptidesmall moleculepolyester amide microsphereintervertebral disk degeneration |
| spellingShingle | Imke Rudnik-Jansen Jie Du Nina Karssemakers-Degen Anna R. Tellegen Parvesh Wadhwani Daniele Zuncheddu Björn P. Meij Jens Thies Pieter Emans Fetullah C. Öner George Mihov Joao Pedro Garcia Anne S. Ulrich Sibylle Grad Marianna A. Tryfonidou Hugo van Ingen Laura B. Creemers Drug retention after intradiscal administration Drug Delivery Drug retention peptide small molecule polyester amide microsphere intervertebral disk degeneration |
| title | Drug retention after intradiscal administration |
| title_full | Drug retention after intradiscal administration |
| title_fullStr | Drug retention after intradiscal administration |
| title_full_unstemmed | Drug retention after intradiscal administration |
| title_short | Drug retention after intradiscal administration |
| title_sort | drug retention after intradiscal administration |
| topic | Drug retention peptide small molecule polyester amide microsphere intervertebral disk degeneration |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2024.2415579 |
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