Study on chitosan/carrageenan core-shell nanoparticles for oral co-administration of insulin/exenatide enhance insulin secretion in type 2 diabetes.

This study developed and evaluated the feasibility of using core-shell chitosan and carrageenan nanoparticles for insulin and exenatide dual-delivery to control blood glucose levels in type 2 diabetes model. Core-shell nanoparticles were fabricated using the coaxial electrospraying technique, exploiting the electrostatic interactions between components to achieve controlled drug release in physicological media. Experimental results indicated that the prepared nanoparticles demonstrated proper physicochemical properties of an oral delivery system, including a hydrodynamic diameter around 300 nm, fitting well through the digestive wall and remaining somewhat stable in the physiologic milieu throughout time, and exhibited non-toxicity to multiple cell lines. The in vitro drug release approximately 80% from the nanoparticles was triggered by pH-sensitive behavior and controlled in spatiotemporal manners in simulated intestinal fluids with digestive enzymes, resulting in inhibition of premature release and self-sustained drug delivery. In type 2 diabetic mice, a single dose (100 IU kg) of nanoparticle generated a pronounced hypoglycemic response, achieving approximately a 45% reduction in blood glucose levels following 4 h oral administration and maintaining insulin plasma at a low level within 12 h owing to insulin and exenatide synergic stimulation effects. Remarkably, treatment with this nanoparticle significantly preserved pancreatic islets and averted type 2 diabetes complications within major organs such as the heart, liver, and kidneys, while maintaining an excellent systemic safety profile. This study evidenced that the nanoparticle-loaded insulin and exenatide were an encouraging long-acting formulation and validated a novel strategy to overcome multiple absorption barriers using polyelectrolyte complex nanoparticles from chitosan and carrageenan.