&NA; The application of dexamethasone releasing poly (lactic‐co‐glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coatings have been successfully used in the suppression of the foreign… Click to show full abstract
&NA; The application of dexamethasone releasing poly (lactic‐co‐glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coatings have been successfully used in the suppression of the foreign body response (FBR) to implantable glucose sensors. In the current study, dexamethasone‐loaded PLGA microspheres were prepared by blending two types of PLGA polymers (RG503H and DLG7E with MW of ca. 25 kDa and 113 kDa, respectively) to achieve long‐term (6 months) inhibition of the FBR. The microsphere composition was optimized according to the in vitro drug release profiles. Microspheres with DLG7E/RG503H/dexamethasone = 70/13.3/16.7 wt% composition, when embedded in a PVA hydrogel, provided a continuous drug release for 6 months. By combining the aforementioned microspheres with microspheres composed solely of the DLG7E polymer within a similar PVA hydrogel realized an even longer (>7 months) in vitro drug release. A heat map was constructed to depict the daily in vitro drug released and elucidate possible lag phases that could affect the pharmacodynamic response. These drug‐loaded implant coatings were investigated in vivo (rat model) and showed inhibition of the foreign body response for 6 months. These results suggest that the minimum effective daily dose to counter chronic inflammation is ca. 0.1 &mgr;g per mg of coating surrounding a 0.5 × 0.5 × 5 mm silicon implant (dummy sensor). Accordingly, these drug‐eluting composite coatings can ensure long‐term inflammation control for miniaturized implantable devices.
               
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