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Dernière publication 02/09/2025

Evaluation of peripheral analgesia in a rat incisional pain model using degradab

To target peripheral opioid receptors for postoperative pain relief while minimizing systemic opioid side effects, low doses of buprenorphine...

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    [title] => Evaluation of peripheral analgesia in a rat incisional pain model using degradab
    [paragraph] => Evaluation of peripheral analgesia in a rat incisional pain model using degradable hydrophilic microspheres for sustained delivery of buprenorphine
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Authors
Laurent Bédouet, Anne Beilvert, Emeline Servais, Florentina Pascale, Saïda Homayra Ghegediban, Michel Wassef, Julien Namur, Laurence Moine

 Lab

Journal
Journal of Materials Chemistry B
Abstract
To target peripheral opioid receptors for postoperative pain relief while minimizing systemic opioid side effects, low doses of buprenorphine hydrochloride (0.8 up to 4.8 mg mL−1) were loaded into prefabricated, hydrophilic, degradable polyethylene glycol-based micropheres (PEG-MS, 50–100 μm) used as a drug delivery platform. By varying the composition of the degradable crosslinker, the degradation rate of PEG-MS, and consequently the drug release duration, could be tuned from 2 days to 2 months. In a pharmacokinetic study in rabbits, the time to the last quantifiable serum concentration (Tlast) of buprenorphine increased with the degradation time of PEG-MS, reaching 1, 2, 4, and 7 days for microspheres degrading over 2, 6, 12, and 50 days, respectively. PEG-MS demonstrated good biocompatibility, as evidenced by only mild and transient local inflammatory responses during their degradation when implanted in various rabbit tissues, including the dermis, muscle, and subconjunctival space. In a rat incisional pain model, the intraplantar injection of buprenorphine-loaded PEG-MS (degrading over 12 days) at doses of 240 μg and 40 μg increased the paw withdrawal threshold at 24 h by 34% (p< 0.0001) and 20% (p= 0.0466), respectively, compared to drug-free microspheres. Serum concentrations of buprenorphine exceeded the therapeutic threshold, indicating that intraplantar administration resulted in systemic, rather than local, effects. In the context of the opioid crisis, the local administration of a degradable drug delivery system that releases a small amount of buprenorphine in an operative wound for a few days after surgery seems relevant. Nevertheless, while the PEG-MS as buprenorphine delivery system was effective, this preliminary study showed that their local administration resulted in the opioid spreading throughout the body. The future of peripheral analgesia lies in developing opioids with physicochemical properties that prevent them from reaching the brain or being active there.
Keywords/Topics
analgesia
BIOSEB Instruments Used:
Electronic Von Frey - Wireless (BIO-EVF-WRS),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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Cet instrument électronique précis et simple d'utilisation est le test de référence pour vos recherches en analgésie, nociception, neuropathies et douleurs post-opératoires

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L'EVF5 intègre une caméra embarquée au niveau de la zone de stimulation et fonctionne avec un nouveau logiciel dédié révolutionnaire

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