Proliposomal Local Anaesthetic Shows Promise for Longer-Lasting Pain Relief

A new “proliposomal” preparation of the local anaesthetic drug ropivacaine may provide a valuable new option for pain relief in some clinical situations, according to a study published in the journal Anesthesia & Analgesia.

Proliposomal ropivacaine can deliver long-lasting pain relief with a single injection, with easier preparation and storage than current slow-release local anaesthetic products.

The new formulation was developed and tested by Yehuda Ginosaur, MD, Hadassah Hebrew University Medical Center, Jerusalem, Israel, and colleagues.

Liposomal local anaesthetics are currently available, but have some important limitations. They are complicated and expensive to manufacture and have a short shelf-life — less than 1 or 2 months, even with refrigeration.

To address these shortcomings, the researchers developed the new proliposomal ropivacaine oil. Comparatively easy to prepare, proliposomal ropivacaine oil can be stored at room temperature for up to 2 years. Liposomes appear, and begin releasing their ropivacaine contents, only when the oil comes into contact with aqueous solutions, including blood plasma.

The researchers initially tested proliposomal ropivacaine in pigs, showing that it gradually released ropivacaine into the animals’ circulation. Ropivacaine levels persisted, along with effective control of pain behaviours, for up to 4 days after application to a surgical wound.

The researchers then tested the new formulation in human volunteers. Subjects were injected with proliposomal or plain ropivacaine at separate locations in the lower back. While the amount injected was the same, the ropivacaine concentration of the proliposomal formulations was 8 times higher (4% vs 0.5%).

The proliposomal product provided much longer-lasting pain control. Anaesthesia to pinprick pain lasted an average of 29 hours with proliposomal ropivacaine injection, compared with 16 hours with plain ropivacaine. For heat pain, the difference was 36 versus 12 hours.

Peak levels of ropivacaine in the circulation were similar between groups, even though the drug concentration was 8 times higher for the proliposomal product. At all times, ropivacaine concentrations remained well below toxic levels.

The prolonged effects of proliposomal ropivacaine — along with its delayed elimination and prolonged redistribution in the circulation — were typical of other types of slow-release local anaesthetic products.

“The advantage of this novel proliposomal ropivacaine is its ease of preparation and extended shelf-life stability at room temperature,” the authors wrote.

In an accompanying editorial, Timothy E. Morey, MD, University of Florida, Gainesville, Florida, pointed out the need for further studies to test the advantages of the new proliposomal formulation, especially in clinical situations where its properties may be most useful. For example, proliposomal ropivacaine might be an effective alternative to the use of perineural catheters for repeated local anaesthetic injections.