New Drug Delivery System Extends Release of Local Anesthetic for Weeks

Local anesthetics used for nerve blocks often provide pain relief for only a limited period, while perioperative pain can persist much longer. Extending the duration of a nerve block therefore requires a delivery system that can control how quickly the anesthetic is released. Researchers have now developed an injectable formulation that sustained local anesthesia in rats for several weeks.

Researchers at Boston Children’s Hospital developed the formulation using multilamellar-multivesicular liposomes made from unsaturated phospholipids. Liposomes are lipid-based structures that can gradually release encapsulated drugs. In the new formulation, double bonds in the lipid tails prevent tight packing, increasing membrane fluidity and promoting the formation of multiple internal compartments rather than simpler spherical structures. These additional lipid barriers slow the release of water-soluble, or hydrophilic, drugs, allowing the formulation to sustain drug delivery over a longer period.

To test the approach, the team loaded the liposomes with tetrodotoxin, a potent neurotoxin that can produce numbness. After injection near a nerve in rats’ legs, the formulation provided local anesthesia for two to three weeks. A commercial formulation lasted about four to eight hours in the comparison reported. No toxicity was observed at the injection site or elsewhere in the body.

The findings were published in Nature Biomedical Engineering on September 23, 2026. Tetrodotoxin is not commercially used in patients, and the prolonged anesthetic effect was demonstrated in rats. The researchers are considering whether this delivery approach could be used for longer-term perioperative pain or chronic pain. They also identified potential use of the liposomes for slow release of other hydrophilic drugs.

“This extended-release combination could be used for longer-term perioperative pain instead of opioids, and we are starting to consider using these potentially for chronic pain as well. These liposomes can also provide slow release of a wide range of hydrophilic molecules,” said Daniel Kohane, MD, PhD, senior associate in pediatric critical care at Boston Children’s Hospital and director of the Laboratory for Biomaterials and Drug Delivery.

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