Chitosan-Based Nanocarriers Co-Delivering Pioglitazone and Curcumin: Biological Activity and Therapeutic Potential in Diabetes.

Diabetes mellitus (DM) is a highly prevalent metabolic disorder and a major public health concern. Pioglitazone, a widely used antidiabetic agent, exhibits limited therapeutic efficiency due to poor water solubility and suboptimal pharmacokinetic properties. Similarly, curcumin (Cur), a natural polyphenol with pleiotropic biological activities, is hindered by low oral bioavailability. In this study, chitosan-based nanocarriers were developed for the delivery of pioglitazone (CS-Pio NPs), curcumin (CS-Cur NPs), and their co-encapsulation (CS-Pio-Cur NPs), aiming to enhance their biological performance and therapeutic efficacy. The co-loaded nanosystem (CS-Pio-Cur NPs) demonstrated significantly enhanced antioxidant activity, as evidenced by DPPH (71.29 ± 0.09%), ABTS (86.08 ± 0.04%), and hydroxyl radical scavenging (87.08 ± 0.06%) assays, along with a strong reducing capacity (IC50 = 25.39 ± 0.23 μg/mL). In a diabetic rat model, CS-Pio-Cur NPs significantly reduced blood glucose level and HbA1c (6.60 ± 0.83%), while also improving liver and kidney function parameters and lipid profile. These findings suggest that co-delivery of Pio and Cur via CS-based nanocarriers provides a combined therapeutic effect by simultaneously targeting hyperglycemia, oxidative stress, and associated metabolic dysfunctions. This nanosystem represents a promising approach for improving the management of DM and its complications.