Biodegradable Polycaprolactone Nanoparticles of Naringin for Improved Anti-Diabetic Potential

Introduction: Naringin, a flavanone glycoside, exhibits significant anti-diabetic potential but suffers from poor aqueous solubility and low bioavailability, limiting its clinical effectiveness. Polycaprolactone (PCL), a biodegradable and biocompatible polymer, offers a promising platform for developing sustained drug delivery systems aimed at enhancing the therapeutic profile of bioactive compounds such as naringin. Objective: This study aimed to develop and characterize naringin-loaded Polycaprolactone Nanoparticles (PCLNPs) to improve drug encapsulation efficiency and stability, enable sustained drug release for prolonged therapeutic effects, evaluate drug release kinetics to understand the release mechanism, and assess the anti-diabetic efficacy of the optimized formulation. results: The average particle size of the naringin-loaded PCLNPs was approximately 206 nm, suitable for efficient absorption and cellular uptake. The nanoparticles exhibited high drug entrapment efficiency ensuring effective drug loading. The formulated nanoparticles showed low zeta potential values, indicating good colloidal stability with minimal risk of aggregation during storage. The nanoparticles exhibited a sustained drug release profile in GI media, following the Higuchi kinetic model. This controlled release behaviour is beneficial for reducing dosing frequency and enhancing patient compliance in diabetes management. FTIR spectra confirmed the successful incorporation of naringin into the nanoparticles without significant chemical interactions, ensuring drug stability and retention of pharmacological activity. The nanoparticles loaded with naringin exhibited significant lowering of blood sugar levels in the diabetic rats as compared to the free naringin at similar dose levels. Methods: Naringin-loaded PCLNPs were prepared using the nanoprecipitation method and optimized based on drug: polymer ratios. Physicochemical characterization included SEM for morphology, DLS for particle size and zeta potential, UV spectrophotometry for encapsulation efficiency and drug loading, FTIR and DSC-TGA for drug-polymer interaction, and in vitro drug release via dialysis. Anti-diabetic activity was evaluated in streptozotocin-induced diabetic Wistar rats over 28 days, with fasting blood glucose measured at regular intervals. Results: The optimized formulation (PCLNPs3, drug: polymer ratio 1:10) showed high encapsulation efficiency (85.40%), drug loading (15.5%), particle size of 130.3 nm, and zeta potential of -42.3 mV. SEM confirmed spherical morphology with a non-porous surface. FTIR and DSC analyses revealed no significant drug-polymer interaction and confirmed successful encapsulation. In vitro drug release showed a sustained profile with 50-62% release over 24 hours and followed Higuchi kinetics (r² > 0.9957) with Fickian diffusion (n < 0.45). In vivo, the naringinloaded PCLNPs reduced fasting blood glucose by 65.5% on Day 28, a value significantly higher than that of free naringin (44.2%) and comparable to that of glipizide. Discussion: The developed PCLNPs effectively improved naringin’s solubility, stability, and anti- diabetic efficacy. The formulation provided controlled release via diffusion mechanisms and prolonged systemic availability. The enhanced hypoglycemic activity of the nanoparticulate formulation can be attributed to improved bioavailability and protection from gastric degradation, demonstrating its suitability for sustained oral delivery in diabetes management.