New Liposome Design Could Provide Effective Slow-Release Drug Delivery System

A new design of liposome for drug delivery could revolutionize the way injectable anesthetics are administered. Current local anesthetics only last between eight hours and a day, but researchers have created a more effective slow-release system that provided pain-numbing effects lasting two to three weeks in rats. This advancement could significantly extend the effectiveness of currently used anesthetics and have implications for other types of pain.

The researchers, led by Yuan Wang, PhD, a research engineer in the laboratory of Daniel Kohane, MD, PhD, discovered that liposomes made of more fluid lipids can release hydrophilic drugs extremely slowly. Hydrophilic drugs mix well with water, but typically leak out of liposomes quickly, resulting in a shorter drug effect and potentially increased toxicity.

Wang challenged this belief by demonstrating that liposomes with more fluid lipids, which have been chemically modified to include many double bonds in their tails, release hydrophilic drugs at a much slower rate.

The secret lies in the structure of these liposomes. The more fluid liposomes formed multiple compartments, which created more lipid barriers for the drugs to pass through, slowing down the release. Wang likens these liposomes to onions with many layers or even spheres within spheres. By slowing the drug release, the researchers were able to achieve potent anesthetic effects without any toxicity at the injection site or throughout the body in rats.

The proof-of-principle experiment used potent tetrodotoxin, a powerful numbing agent found in pufferfish and blue-ringed octopuses. When injected near a nerve in the leg of rats, the liposomes provided prolonged local anesthesia without any adverse effects. Although tetrodotoxin is not currently used in humans, it could potentially be developed as a therapeutic in the future.

This new liposome design has the potential to revolutionize perioperative pain management, offering an extended-release combination that could replace opioids and provide slow-release of a wide range of hydrophilic molecules. The findings were published in Nature Biomedical Engineering in the paper, "Ultra-slow release of hydrophilic drugs via multilamellar–multivesicular liposomes formed by unsaturated phospholipids."