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J Pharm Bioallied Sci. 2014 Jan;6(1):38-42. doi: 10.4103/0975-7406.124315.

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

Journal of pharmacy & bioallied sciences

Michael Guarnieri, Betty M Tyler, Louis Detolla, Ming Zhao, Barry Kobrin

Affiliations

  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.

PMID: 24459402 PMCID: PMC3895292 DOI: 10.4103/0975-7406.124315

Abstract

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.

Keywords: Analgesia; buprenorphine; disintegration; mouse; sustained delivery

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