Evidence map›Paper›PMID 41770921›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Extended local anesthesia enabled by flavonoid permeation enhancers.

Yiyuan Han, Matthew Torre, Xiaojing Ma, Tianrui Xue, Yuan Wang, Sooyeon Jo, Akie Fujita, Bruce P Bean, Daniel S Kohane

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Yiyuan HanLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
Matthew TorreDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030.ORCID 0000-0002-5221-7776
Xiaojing MaLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
Tianrui XueLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
Yuan WangLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-9089-2617
Sooyeon JoDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115.
Akie FujitaDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115.
Bruce P BeanDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-5093-3576
Daniel S KohaneLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.ORCID 0000-0001-5369-5932

Funding

Prolonged duration and triggered local anesthesiaR35GM131728 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI Daniel S Kohane · 2019 to 2026
$5.4M
Ion Channel Pharmacology for Pain and EpilepsyR35NS127216 · NINDS · HARVARD MEDICAL SCHOOL · PI BRUCE P BEAN · 2022 to 2026
$3.6M
HHS | NIH (NIH) R35GM131728HHS | NIH (NIH) R35NS127216NIGMS NIH HHS R35 GM131728NINDS NIH HHS R35 NS127216
6 · The paper itself

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.

Indexed as

Anesthesia, LocalAnesthetics, LocalFlavonoidsAnimalsBioenhancersFlavanonesKaempferolsLiposomesPermeabilityRatsSodium Channel BlockersTetrodotoxinAnesthetics, LocalBioenhancersFlavanonesFlavonoidskaempferolKaempferolsLiposomesnaringeninSodium Channel BlockersTetrodotoxinbiological barrierchemical permeation enhancerdrug deliveryflavonoidlocal anesthesia

Identifiers

PMID41770921
PMCPMC12974474

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.