(413c) Performance of Implantable Glucose Sensors Coated With Dexamethasone-Releasing PLGA Microsphere/PVA Hydrogel Composites

Introduction: Implantable biosensors for continuous glucose monitoring hold promise for Diabetes care and management.  The long-term potential of implantable biosensors is often negated by the foreign body response (biofouling and inflammation), elicited following device implantation.  Herein, we show that outer sensor coatings based on dexamethasone-loaded PLGA microsphere/PVA hydrogel composite improves in vivo sensor performance by (i) suppressing inflammation and fibrosis via sustained delivery of dexamethasone following microsphere degradation; (ii) offsetting biofouling-induced permeability reduction via creation of macroscopic porosity following microsphere degradation.

Materials and Methods: Poly (lactic-co-glycolic) acid (PLGA) microspheres were prepared using a solvent evaporation technique. PVA hydrogels with and without PLGA microspheres were fabricated using a freeze/thaw cycling method. Implantable glucose sensors utilizing enzymatic detection of glucose were coated with dexamethasone -containing PLGA microspheres/poly (vinyl alcohol) (PVA) hydrogel composite.  At first, the effect of the coating on the sensor linearity and sensitivity was determined in vitro (in PBS).  Subsequently, coated and uncoated sensors (controls) were implanted into anesthetized rats using a thin wall needle (16 Gauge) and their sensitivity was determined periodically.  All In vivo experiments were performed in accordance with the IACUC (Institutional Animal Care and Use Committee) guidelines.

Results and Discussion:  In vitro results have indicated that the composite coating does not hinder sensor linearity but reduced sensitivity by 30%.  In vivo studies have indicated that the uncoated biosensors suffered a rapid sensitivity loss in the first week post implantation and eventually failed to track the glycemic events.  On the other hand, the coated sensors reproducibly tracked blood glycemic events even after 14 days following implantation due to the dexamethasone-induced inflammation suppression.  Moreover, the sensitivity of the coated sensors increased with in vivo residence time which is currently attributed to macroscopic porosity generation following microsphere degradation (consistent with our ex vivo studies in porcine serum). 

Conclusions:  The PLGA microsphere/PVA hydrogel composite coatings did not compromise the linearity of the glucose biosensors, albeit formed a additional barrier to analyte diffusion thereby decreasing sensor sensitivity by 30%. In vivo studies indicated that the composite coatings were able to enhance sensor performance and lifetime.  This renders these drug-delivering coatings as a promising vehicle for improving in vivo functionality of implantable biosensors. 

 Acknowledgements: Financial support for this study was obtained from US Army Medical Research Grants (W81XWH-09-1-0711 and W81XWH-07-10688), NIH grants (1-R21-HL090458-01, R43EB011886 and 9R01EB014586) and NSF/SBIR grants (1046902 and 1230148)