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ORIGINAL ARTICLE
Year : 2014  |  Volume : 6  |  Issue : 1  |  Page : 38-42

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs


1 Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
2 Department of Pathology and Medicine, School of Medicine, Division of Infectious Diseases and Public Health, The Program of Comparative Medicine, University of Maryland, Baltimore, Maryland, USA
3 Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Correspondence Address:
Michael Guarnieri
Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland
USA
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Source of Support: Funding for the present study was supplied by the Maryland Industrial Partnership, a State of Maryland fund to promote the development of products and processes through industry/university research partnerships. M. Guarnieri received additional funding from Bamvet, Inc., and holds a significant financial interest in Bamvet. The project described was supported in part by Grant Number UL1 RR 025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH, Conflict of Interest: None


DOI: 10.4103/0975-7406.124315

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Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs.


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