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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)38-42
Number of pages5
JournalJournal of Pharmacy and Bioallied Sciences
Volume6
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Analgesia
  • buprenorphine
  • disintegration
  • mouse
  • sustained delivery

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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