ArticleProceedings of the National Academy of Sciences of the United States of America2026
Extended local anesthesia enabled by flavonoid permeation enhancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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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
1 citing paper in PubMed.
- Peptide Coacervates as Dynamic and Interactive Depots for Tetrodotoxin in Long-Acting Local Anesthesia.Advanced healthcare materials · 2026Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Site 1 sodium channel blockers (S1SCBs), such as tetrodotoxin (TTX) and neosaxitoxin, are ultrapotent local anesthetics with low tissue toxicity. Their duration of action is relatively brief, but increasing the dose can lead to systemic toxicity. Here, we report that selected flavonoids-puerarin (PUE), naringenin, and kaempferol-prolong nerve block from S1SCBs 4- to 25-fold. Using both tympanic membrane (TM) permeation and sciatic nerve fluorescence distribution models, we demonstrate the flavonoids increase drug penetration across biological barriers (the TM and the barriers in and around nerve), suggesting that they act as chemical permeation enhancers (CPEs). Importantly, flavonoids exhibited minimal tissue toxicity compared to conventional CPEs. Coencapsulation of TTX and PUE into a liposomal delivery system further prolonged local anesthesia to over 25 d from a single injection. These findings establish flavonoid compounds as a safe class of CPEs and provide a platform of long-acting, nonopioid pain therapies. Flavonoids may be attractive alternatives to conventional CPEs in biomedical applications.
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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 Socratic graph.