In this proposal, Comfort Care for Animals LLC (CCA) (Madison, WI) will create slow-release (minimum 10-12 days in this Phase, with an ultimate goal of 28 days) injectable liposomal buprenorphine formulation to treat moderate to severe post-surgical or chronic pain in people and animals and to use as a treatment for opioid addiction in people. This innovative new drug-delivery system aims to address the widespread problem of providing long-term, non-divertible opioid pain relief for moderate to severe pain while also eliminating troughs in analgesia. We selected buprenorphine for this application because it is widely used as a maintenance therapy for opioid addiction, and as a treatment for surgical and chronic pain, but our novel delivery system should work with a large variety of additional drugs. This delivery system could provide reliable, long-duration analgesia or withdrawal symptom suppression from a single, monthly injection administered by trained medical professionals, removing a large amount of oral opiates from the pool of potentially-diverted drugs. The two week to month-long duration corresponds well to the typical, clinical schedule of many chronic-pain patients. And, finally, the use of liposomes overcomes the issues of inflammation and allergic reaction that have been associated with microspheres or implants. In Phase I, the investigators will: (1) determine the optimal buprenorphine encapsulation procedure for our proprietary Quantload methodology of at least 75%, (2) determine in vitro release characteristics and product stability as determined by leakage of less than 20% over a period of 1 month, and (3) conduct preliminary pharmacokinetics in vivo in rats. Our preliminary data indicate that Quantload technology produces greater than 90% loading efficiency, with less than 10% leakage in vitro over 4 days, and up to 12 days of serum concentrations greater than 1 ng/mL in rats. In order to demonstrate feasibility of the Quantload delivery system in this Phase I project, we will obtain a repeatable release period of at least 4 weeks in a standard dialysis bag release assay in vitro and a cumulative release of drug in daily samples over that period of less than 20% of the drug and that it can maintain serum concentrations in vivo for a period of up to one month that correlates with analgesic levels. In so doing, we will demonstrate the feasibility of a commercially-viable liposomal buprenorphine product that may be marketed either for chronic pain or addiction treatment. Both physicians and veterinarians will gain a new treatment tool that requires fewer doses and provides better pain relief or control of drug cravings when compared to current methods. This will offer positive benefits of reduced costs associated with reduced personnel time for treatments, better pain treatment for patients that eliminates troughs associated with oral dosing regimens, and elimination of opioid diversion or accidental exposure in the patient's environment.
The purpose of this project is to formulate and study a single-injection, up to 28-day release liposomal formulation of the opioid analgesic buprenorphine for relief of post- surgical and chronic pain in human beings and animals. The commercial availability of this product would considerably improve chronic pain treatment by giving physicians an option that continuously treats pain without peaks and valleys associated with oral medications. This product could also be used for treatment of opioid addiction, and its use would decrease the amount of opioid medications available for criminal diversion.