Controlled release of dexamethasone from subcutaneously‐implanted biosensors in pigs: Localized anti‐inflammatory benefit without systemic effects

Abstract

Chronically implanted biosensors typically lose sensitivity 1–2 months after implantation, due in large part to the development of a collagen‐rich capsule that prevents analytes of interest from reaching the biosensor. Corticosteroids are likely candidates for reducing collagen deposition but these compounds have many serious side effects when given over a prolonged period. One method of assessing whether or not locally released corticosteroids have a systemic effect is to measure cortisol concentrations in venous serum. We hypothesized that a very low release rate of the potent corticosteroid, dexamethasone, would lead to a localized anti‐inflammatory effect without systemic effects. We found that reduction in subcutaneous granulocytes (primarily eosinophils), and to a lesser extent, reduction of macrophages served as a good local indicator of the steroid effect. When released over a 28‐day period, a total dexamethasone dose of ≤0.1 mg/kg led to a consistent reduction in the number of granulocytes and macrophages found in the local vicinity of the implant without a reduction of these cells at distant tissue locations. The lack of suppression of serum cortisol with these doses confirmed that low‐release rates of dexamethasone can lead to consistent local anti‐inflammatory effects without distant, systemic effects. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010