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

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.