ArticleNature communications2019
Polymer-tetrodotoxin conjugates to induce prolonged duration local anesthesia with minimal toxicity.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Comparative effectiveness of nerve block strategies for preventing postherpetic neuralgia in thoracic herpes zoster: a network meta-analysis.Frontiers in neurology · 2025Pooled it
- Ultra-slow release of hydrophilic drugs via multilamellar-multivesicular liposomes formed by unsaturated phospholipids.Nature biomedical engineering · 2026Article
- Peptide Coacervates as Dynamic and Interactive Depots for Tetrodotoxin in Long-Acting Local Anesthesia.Advanced healthcare materials · 2026Article
- Polymeric rapamycin nanoparticles encapsulating ponatinib cause regression of venous malformations in mice.Science translational medicine · 2026Article
- Extended osteoarthritis pain relief with neosaxitoxin using alginate-core polymeric microparticles.Nanoscale · 2025Article
- Injectable Microparticle-Nanoliposome Hydrogel for Extended Release of Small Hydrophilic Molecules.ACS nano · 2025Article
- Enhanced Control of Liposomal Drug Release by Drug-Aptamer Complexes.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- The Chemistry and Biology of the Tetrodotoxin Natural Product Family.Angewandte Chemie (International ed. in English) · 2025Review
- Review
- Glucose-Facilitated Nanomicelles Cross Peripheral Nerve Barriers to Achieve Drug Delivery to Nerves.Advanced functional materials · 2025Article
- Tetrodotoxin Delivery Pen Safely Uses Potent Natural Neurotoxin to Manage Severe Cutaneous Pain.Advanced healthcare materials · 2025Article
- Molecular Dynamics Insights into Peptide-Based Tetrodotoxin Delivery Nanostructures.Molecules (Basel, Switzerland) · 2024Article
- 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
- Nanomedicine and voltage-gated sodium channel blockers in pain management: a game changer or a lost cause?Drug delivery and translational research · 2024Review
- Polymeric Prodrugs using Dynamic Covalent Chemistry for Prolonged Local Anesthesia.Angewandte Chemie (International ed. in English) · 2024Article
- Galacturonic acid-capsaicin prodrug for prolonged nociceptive-selective nerve blockade.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.Current pain and headache reports · 2024Review
- Marine Toxins as Pharmaceutical Treasure Troves: A Focus on Saxitoxin Derivatives from a Computational Point of View.Molecules (Basel, Switzerland) · 2024Article
- Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia.Theranostics · 2024Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
There is clinical and scientific interest in developing local anesthetics with prolonged durations of effect from single injections. The need for such is highlighted by the current opioid epidemic. Site 1 sodium channel blockers such as tetrodotoxin (TTX) are extremely potent, and can provide very long nerve blocks but the duration is limited by the associated systemic toxicity. Here we report a system where slow release of TTX conjugated to a biocompatible and biodegradable polymer, poly(triol dicarboxylic acid)-co-poly(ethylene glycol) (TDP), is achieved by hydrolysis of ester linkages. Nerve block by the released TTX is enhanced by administration in a carrier with chemical permeation enhancer (CPE) properties. TTX release can be adjusted by tuning the hydrophilicity of the TDP polymer backbone. In vivo, 1.0-80.0 µg of TTX released from these polymers produced a range of durations of nerve block, from several hours to 3 days, with minimal systemic or local toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.