Proliposomal ropivacaine may offer valuable new option for pain relief

Apr 15 2016

A new "proliposomal" preparation of the local anesthetic drug ropivacaine may provide a valuable new option for pain relief in some clinical situations, with key advantages over other types of slow-release local anesthetics, suggest a pair of reports in Anesthesia & Analgesia.

Proliposomal ropivacaine can deliver long-lasting pain relief with a single injection, with easier preparation and storage than current slow-release local anesthetic products, according to initial studies in animals and human volunteers. The new formulation was developed and tested by Dr. Yehuda Ginosaur of Hadassah Hebrew University Medical Center, Jerusalem, and colleagues.

New Product Doesn't Become 'Liposomal' Until It's Injected
Liposomal preparations are used as a way of delivering controlled-release of drugs or other products (for example, cosmetics). Liposomes are nano-sized "bubbles" that release their contents as they dissolve. Liposomal local anesthetics are currently available, but have some important limitations. They are complicated and expensive to manufacture and have a short shelf-life—less than one or two months, even with refrigeration.

To address these shortcomings, Dr. Ginosaur and colleagues developed the new "proliposomal" ropivacaine oil. Comparatively easy to prepare, proliposomal ropivacaine oil can be stored at room temperature for up to two years. Liposomes appear, and begin releasing their ropivacaine contents, only when the oil comes into contact with aqueous (water-containing) 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 behaviors, for up to four days after application to a surgical wound.

Dr. Ginosaur and colleagues then proceeded to studies in human volunteers, who 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 eight times higher: four percent versus 0.5 percent.

The proliposomal product provided much longer-lasting pain control. Anesthesia to pinprick pain lasted an average of 29 hours with proliposomal ropivacaine injection, compared to 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 eight 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 anesthetic products. "The advantage of this novel proliposomal ropivacaine is its ease of preparation and extended shelf-life stability (>2 years) at room temperature," Dr. Ginosaur and coauthors write.

In an accompanying editorial, Dr. Timothy E. Morey of University of Florida points 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 anesthetic injections.

"This is an important advance over existing liposomal preparations, comments Dr. Steven L. Shafer of Stanford University, Editor-in-Chief of Anesthesia & Analgesia. "Proliposomal products could significantly extend the duration of pain control after infiltration of local anesthetics—a worthy but so far elusive goal."