ArticleJournal of controlled release : official journal of the Controlled Release Society2024
Galacturonic acid-capsaicin prodrug for prolonged nociceptive-selective nerve blockade.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Spontaneous Non-Catalyzed Molecular Reactions and Interactions in the Human Body: Biomedical Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Carboxylated prodrug of capsaicin with enhanced peripheral nerve permeation mediated by monocarboxylate transporters for long-lasting local anesthesia.Acta pharmaceutica Sinica. B · 2026Article
- Glucose-Facilitated Nanomicelles Cross Peripheral Nerve Barriers to Achieve Drug Delivery to Nerves.Advanced functional materials · 2025Article
- Capsaicin-Loaded Melanin Nanoparticles for Long-Lasting Nociceptive-Selective Nerve Blockade.Langmuir : the ACS journal of surfaces and colloids · 2024Article
- Exosomal Bupivacaine: Integrating Nerve Barrier Penetration Capability and Sustained Drug Release for Enhanced Potency in Peripheral Nerve Block and Reduced Toxicity.Advanced functional materials · 2024Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.
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Registered trials
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