Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control.
BACKGROUND
Successful performance of implantable glucose biosensors for metabolic monitoring is dependent on tissue compatibility. Negative immunostimulatory tissue reactions that occur due to implantation-induced tissue injury and the prolonged presence of such sensors can lead to a loss of functionality and device failure. The use of novel poly(lactic-co-glycolic) acid (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composite coatings for implantable biosensors to control localized inflammation and fibrosis at the sensor/tissue interface is reported.


METHODS
Dexamethasone-loaded PLGA microspheres were prepared using a solvent evaporation technique. Composites were fabricated by dispersing microspheres in PVA solution and performing freeze-thaw cycling. Composites were implanted into subcutaneous tissue of rats. In vitro and in vivo drug release kinetics were studied. Immunostimulatory response was determined through histopathological evaluation of excised tissue.


RESULTS
PLGA microsphere/PVA hydrogel composites achieved localized dexamethasone delivery with approximate zero-order release kinetics. A linear level A in vitro-in vivo correlation was observed (R2 = 0.97). Dexamethasone released at a steady rate of 0.17 microg/day was sufficient to control acute and chronic inflammation as well as fibrosis. Implantation of composites containing no drug led to significant infiltration of inflammation-mediating cells at the implant site characteristic of acute inflammation followed by proliferation of a fibrotic band surrounding the implant by week 3.


CONCLUSIONS
PLGA microsphere/PVA hydrogel composites eluting dexamethasone were successful in controlling negative tissue reactions at the sensor-tissue interface by reducing the level of inflammation-mediation cells to those observed in normal tissue. These composites show promise as coatings for implantable biosensors to improve biocompatibility and prolong sensor lifetime.
Patil
Siddhesh D
SD
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269, USA.
Papadimitrakopoulos
Fotios
F
Burgess
Diane J
DJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019344:Lactic Acid; D008863:Microspheres; D023421:Models, Animal; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011142:Polyvinyl Alcohol; D051381:Rats; D014481:United States
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D011142:Polyvinyl Alcohol