pH-Responsive Glycosylated PC Nanoparticles for Oral Insulin Delivery.

Oral insulin delivery represents a compelling alternative to conventional injections because of its enhanced patient compliance and administration convenience. However, this approach faces substantial challenges stemming from physiological barriers that include the gastrointestinal environment, mucus layer obstruction, and poor intestinal absorption. To overcome these limitations, we designed glycosylated proanthocyanidin (PC) nanoparticles using a sacrificial ZIF-8 template for insulin encapsulation. The resulting nanoparticles achieved high loading efficiency and combined two critical functions: gastric protection and enhanced intestinal absorption. Specifically, the nanoparticles preserved insulin stability under acidic gastric conditions and released their payload in response to physiological pH. Furthermore, surface glucose modifications significantly improved the cellular uptake through specific interactions with glucose transporters. When evaluated in a type 1 diabetic mouse model, this Ins@PC@PEG-Glu nanoparticle system showed markedly better therapeutic effects with 7.9% bioavailability, demonstrating its strong potential as an oral insulin delivery platform.