# Optimization of Controlled-Release Microspheres Containing Vitexin and Isovitexin Through Experimental Design and Evaluation of Their Hypoglycemic Effects

## TL;DR

This study develops microspheres to improve the delivery and effectiveness of vitexin and isovitexin, showing they can lower blood sugar in diabetic mice.

## Contribution

A novel alginate–chitosan microsphere formulation for controlled release of vitexin and isovitexin with optimized properties and hypoglycemic effects.

## Key findings

- Optimized microspheres had a mean size of 10.78 µm, 22.45% loading ratio, and 68.92% encapsulation efficiency.
- The microspheres released vitexin–isovitexin in a controlled manner within 24 hours in vitro.
- The microspheres showed hypoglycemic effects in diabetic mice by improving pancreatic β-cell function and insulin resistance.

## Abstract

Background/Objectives: Vitexin and isovitexin are bioactive flavonoids with promising pharmacological effects; however, they have poor bioavailability. Microencapsulation with biodegradable polymers is a promising strategy for improving their stability, bioavailability, and biocompatibility. This study aimed to optimize the formulation parameters to obtain microspheres with desired properties in terms of size, loading ratio, and vitexin–isovitexin release. Methods: Microspheres were prepared using alginate as the core matrix and a chitosan outer layer. A Design of Experiment approach using response surface methodology was employed. The hypoglycemic effects of the obtained microspheres were evaluated. Results: The formulation using 1.17% low-viscosity alginate, 7.60% calcium chloride, 5.78% Tween 80, and 5.00% Span 80 resulted in microspheres with optimal mean size (10.78 µm), high loading ratio (22.45%) and encapsulation efficiency (68.92%). The in vitro release of vitexin–isovitexin from microspheres was completed within 24 h in controlled manner. The microspheres were found to be non-toxic in vivo and exhibited hypoglycemic effects after 21 days at doses equivalent to 30 and 60 mg/kg of vitexin–isovitexin. The potential mechanisms might involve increasing the size of Islets of Langerhans and improving pancreatic β-cell function and insulin resistance, as observed in alloxan-induced diabetic mice. Conclusions: This work successfully developed alginate–chitosan-based microspheres for the controlled release of vitexin–isovitexin while maintaining their bioactivities.