Insulin Granule-Loaded MicroPlates for Modulating Blood Glucose Levels in Type-1 Diabetes.

ABSTRACT

Type-1 diabetes (T1DM) is a chronic metabolic disorder resulting from the autoimmune destruction of ß cells. The current standard of care requires multiple, daily injections of insulin and accurate monitoring of blood glucose levels (BGLs); in some cases, this results in diminished patient compliance and increased risk of hypoglycemia. Herein, we engineered hierarchically structured particles comprising a poly(lactic-co-glycolic) acid (PLGA) prismatic matrix, with a 20 × 20 µm base, encapsulating 200 nm insulin granules. Five configurations of these insulin-microPlates (INS-µPLs) were realized with different heights (5, 10, and 20 µm) and PLGA contents (10, 40, and, 60 mg). After detailed physicochemical and biopharmacological characterizations, the tissue-compliant 10H INS-µPL, realized with 10 mg of PLGA, presented the most effective release profile with ∼50% of the loaded insulin delivered at 4 weeks. In diabetic mice, a single 10H INS-µPL intraperitoneal deposition reduced BGLs to that of healthy mice within 1 h post-implantation (167.4 ± 49.0 vs 140.0 ± 9.2 mg/dL, respectively) and supported normoglycemic conditions for about 2 weeks. Furthermore, following the glucose challenge, diabetic mice implanted with 10H INS-µPL successfully regained glycemic control with a significant reduction in AUC0-120min (799.9 ± 134.83 vs 2234.60 ± 82.72 mg/dL) and increased insulin levels at 7 days post-implantation (1.14 ± 0.11 vs 0.38 ± 0.02 ng/mL), as compared to untreated diabetic mice. Collectively, these results demonstrate that INS-µPLs are a promising platform for the treatment of T1DM to be further optimized with the integration of smart glucose sensors.