Intestine-Settled Electrospun Short-Fibers Modulate Epithelial Transport Proteins to Reduce Purine and Glucose Uptake

Abstract

Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia, mediated by specific intestinal transport proteins. Currently, there is a deficiency in targeted regulation of these proteins. In this study, we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa. These fibers, designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin. Phlorizin is conjugated via a phenyl borate ester bond. Furthermore, a calcium alginate shell ensures intestinal disintegration triggered by pH changes. These fibers adhere to the mucosa due to their unique structure, and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond, enabling dual-target inhibition of intestinal transporter proteins. Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties, facilitating precise control over transport proteins. Using models of hyperuricemia and diabetes in mice, treatment with short-fibers results in reductions of 49.6% in blood uric acid and 17.8% in glucose levels, respectively. Additionally, 16S rRNA sequencing indicates an improved intestinal flora composition. In conclusion, we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.

Graphical abstract