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.


CONCLUSIONS
The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space.


CONCLUSIONS
Drug implants can retain significant and unintended reservoirs of drugs.
Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Michael
M
Guarnieri
Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Betty M
BM
Tyler
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.
Louis
L
Detolla
Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Ming
M
Zhao
Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Barry
B
Kobrin
Analgesia; buprenorphine; disintegration; mouse; sustained delivery