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Drug retention after intradiscal administration

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Title: Drug retention after intradiscal administration
Authors: Rudnik-Jansen, Imke, Du, Jie, Karssemakers-Degen, Nina, Tellegen, Anna R., Wadhwani, Parvesh, Zuncheddu, Daniele, Meij, Björn P., Thies, Jens, Emans, Pieter, Öner, Fetullah C., Mihov, George, Garcia, Joao Pedro, Ulrich, Anne S., Grad, Sibylle, Tryfonidou, Marianna A., Ingen, Hugo van, Creemers, Laura B.
Contributors: Orthopaedie Onderzoek, ORT Research, Regenerative Medicine and Stem Cells
Source: Drug Deliv
Drug Delivery, Vol 31, Iss 1 (2024)
Drug Delivery, 31 (1), Art.-Nr.: 2415579
Publisher Information: Informa UK Limited, 2024.
Publication Year: 2024
Subject Terms: Male, POLY(ESTER AMIDE)S, ddc:540, Chemistry & allied sciences, Polyesters, small molecule, RM1-950, Intervertebral Disc Degeneration, Peptides/chemistry, polyester amide microsphere, Rats, Sprague-Dawley, MICROSPHERES, Drug Delivery Systems, INFLAMMATION, CARTILAGE, DELIVERY-SYSTEMS, Journal Article, Drug Delivery Systems/methods, EXTRACELLULAR-MATRIX, Intervertebral Disc/drug effects, Animals, Intervertebral Disc Degeneration/drug therapy, Intervertebral Disc, Polyesters/chemistry, NEEDLE PUNCTURE, intervertebral disk degeneration, HUMAN INTERVERTEBRAL DISC, DEGENERATION, peptide, Microspheres, Rats, MODEL, Sprague-Dawley, Therapeutics. Pharmacology, Peptides, Hydrophobic and Hydrophilic Interactions, Drug retention, Research Article
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.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1521-0464
1071-7544
DOI: 10.1080/10717544.2024.2415579
DOI: 10.5445/ir/1000176080
Access URL: https://pubmed.ncbi.nlm.nih.gov/39427239
https://doaj.org/article/e74ff26b3ae344bf99b69a5fc7b3d7c3
https://research-portal.uu.nl/en/publications/b6364710-36b4-4536-b365-835cf069570c
https://doi.org/10.1080/10717544.2024.2415579
https://dspace.library.uu.nl/handle/1874/458454
https://publikationen.bibliothek.kit.edu/1000176080
https://publikationen.bibliothek.kit.edu/1000176080/155465782
https://doi.org/10.5445/IR/1000176080
Rights: CC BY NC
URL: http://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
URL: http://creativecommons.org/licenses/by-nc/4.0/deed.de
Accession Number: edsair.doi.dedup.....0620a11dfd9fd15aec6b2f4efdf217e4
Database: OpenAIRE
Description
Abstract: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.
ISSN:15210464
10717544
DOI:10.1080/10717544.2024.2415579