Drug retention after intradiscal administration

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Drug Delivery, Vol 31, Iss 1 (2024)
Druh dokumentu: article
ISSN: 10717544
1521-0464
1071-7544
DOI: 10.1080/10717544.2024.2415579
Popis: 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.
Databáze: Directory of Open Access Journals
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