title: 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 < or =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. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
authors.affiliation: Legacy Health System, Portland, Oregon, USA. kward@legacyglucosesensor.org
authors.forename: W Kenneth
authors.initials: WK
authors.lastname: Ward
authors.forename: Jillian C
authors.initials: JC
authors.lastname: Hansen
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Massoud
authors.forename: Julia M
authors.initials: JM
authors.lastname: Engle
authors.forename: Marc M
authors.initials: MM
authors.lastname: Takeno
authors.forename: Kip D
authors.initials: KD
authors.lastname: Hauch
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000627:therapeutic use; D015374:Biosensing Techniques / Q000295:instrumentation; D003907:Dexamethasone / Q000378:metabolism* / Q000627:therapeutic use; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D020007:Implants, Experimental; D008264:Macrophages / Q000166:cytology; D034421:Sus scrofa
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D006854:Hydrocortisone