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Journal of Veterinary Medicine
Volume 2017 (2017), Article ID 3102567, 11 pages
https://doi.org/10.1155/2017/3102567
Research Article

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

1Johns Hopkins School of Medicine, Department of Neurological Surgery, Baltimore, MD, USA
2Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology, Baltimore, MD, USA
3George Mason University, Fairfax, VA, USA
4University of Maryland School of Medicine, Departments of Pathology, Medicine, Epidemiology and Public Health and the Program of Comparative Medicine, Baltimore, MD, USA

Correspondence should be addressed to M. Guarnieri

Received 14 January 2017; Revised 18 March 2017; Accepted 21 March 2017; Published 9 April 2017

Academic Editor: Vito Laudadio

Copyright © 2017 M. Guarnieri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.