The New Anesthesia That Can Last Weeks Instead of Hours

A new controlled-release technology has succeeded in keeping an anesthetic active on a nerve for two to three weeks in rats. The strategy employs tiny fat-based structures that store the medication and hinder its rapid release, keeping it concentrated at the application site.

A local anesthetic that typically lasts only a few hours could, in the future, remain active for weeks. Scientists have developed small fat-based structures capable of carrying medications and slowly releasing them at the site of application.

In tests involving rats, one of these formulations maintained a nerve block for two to three weeks without causing signs of toxicity elsewhere in the body. This discovery could pave the way for treatments requiring a medication to remain concentrated in a specific region for a much longer period.

The challenge stems from the inherent behavior of certain medications. When a drug is applied to a specific part of the body, it can rapidly spread through tissues and enter the bloodstream. This is particularly problematic for medications that mix easily with water, known as hydrophilic drugs.

To try to keep these drugs in place, researchers used liposomes, small structures formed by fat molecules. They function like tiny capsules: the drug is stored inside and, ideally, is gradually released into the tissue near the application site.

To determine which type of liposome would work best, scientists produced different versions of these capsules under identical conditions. The main difference lay in the fat molecules used to form their membranes. Some featured more rigid molecules, while others contained small chemical alterations known as unsaturations, which made the molecules less rigid. The initial expectation was that a less rigid membrane would allow the drug to escape more quickly. However, the opposite occurred.

The four types of liposomes used

Liposomes formed from the fat known as DOPC managed to store about three times more medication, released approximately 11 times less medication immediately after application, and, even after seven days, continued to release the drug much more slowly than the more rigid liposomes.

The researchers then investigated the reasons behind this. Upon analyzing the structures formed by the liposomes, they observed that the particles did not simply remain as small, isolated capsules. Many organized themselves into larger structures containing multiple layers or several small pockets of medication. This arrangement created more space for drug storage while simultaneously hindering rapid release.

The scientists repeated the experiments using different water-soluble drugs and observed the same behavior. This suggested that the effect was not dependent on a specific substance but could be a characteristic of the liposome structure itself.

Finally, the researchers tested the strategy on rats. They loaded the liposomes with tetrodotoxin, a substance capable of temporarily blocking the transmission of electrical signals along nerves. Instead of rapidly dissipating from the application site, the encapsulated substance continued to act on the nerve for two to three weeks, resulting in a prolonged block. At the same time, the researchers observed no signs of systemic toxicity, that is, significant toxic effects caused by the drug reaching other parts of the body.

These results are still experimental and were obtained in animal studies, but they demonstrate a relatively simple way to transform short-acting drugs into treatments capable of remaining concentrated at a specific site for a much longer period.

READ MORE:

Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids

Yuan Wang, Tianrui Xue, Matthew Torre, Yiyuan Han, Rachelle Shao, and Daniel S. Kohane

Nature Biomedical Engineering. 23 September 2026DOI: 10.1038/s41551-026-01793-6

Abstract: 

Maintaining therapeutic drug concentrations at a target site while limiting systemic exposure is difficult for hydrophilic drugs, which rapidly diffuse from the injection site. Liposomes are widely used carriers, yet designs based on rigid, saturated phospholipids aim to reduce membrane permeability but often yield modest loading and substantial burst release. Here we compared liposomes composed of phospholipids of identical chain length but varying unsaturation, prepared under matched conditions. Contrary to the expectation that unsaturation accelerates release, liposomes based on 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) showed approximately 3-fold higher loading, 11-fold lower initial release and 4-fold lower release at 7 days than saturated analogues. These effects correlated with the emergence of multilamellar and multivesicular structures and extended across diverse hydrophilic drugs. In a rat sciatic nerve block model, tetrodotoxin-loaded liposomes produced 2–3 weeks of blockade without systemic toxicity, establishing a simple platform for sustained local delivery.