%0 Journal Article
%T Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice
%A L. DeTolla
%A R. Sanchez
%A E. Khan
%A B. Tyler
%A M. Guarnieri
%J Journal of Veterinary Medicine
%D 2014
%R 10.1155/2014/365673
%X Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3£¿mg/kg dose of drug. One male mouse treated with three 3£¿mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. 1. Introduction Guidelines for the care and use of laboratory animals uniformly recommend the use of analgesia in any procedure with a potential for pain [1]. Yet, the use of analgesics in research remains low [2, 3]. One factor that may account for the modest utilization of analgesia is the management challenge involved with intraperitoneal (IP) and subcutaneous (SC) injections of mice and rats at the 6¨C8-hour intervals necessary to maintain effective blood concentrations of drug [4]. In addition, it has been considered that repeated IP or SC injections in surgically traumatized rodents may induce stress responses and depress weight gain [5, 6]. Several strategies are being investigated to address this problem. The practicality and duration of slow-release oral preparations for 11-hour morphine therapy in laboratory rats have been described [7]. Food- and water-based analgesia has been explored by several investigators [8¨C10]. Grant and colleagues demonstrated that liposomal morphine implants could deliver long-acting analgesia to mice [11]. More recently, Smith, Krugner-Higby, and colleagues have published a series of studies demonstrating the 2-3-day activity of lipid encapsulated morphine derivatives in laboratory animal models of pain [12¨C14]. Foley and colleagues described the 2-3-day efficacy of a proprietary sustained release polymer-based buprenorphine preparation in rats [15]. Carbone and coworkers described the efficacy of a similar formulation
%U http://www.hindawi.com/journals/jvm/2014/365673/