Site-specific adaptive nanovesicles for oral insulin delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Oral insulin delivery faces challenges due to the gastrointestinal environment, intestinal permeability, and liver clearance.
• Improving patient compliance is a key goal for insulin therapy.

Purpose of the Study:

• To develop site-specific adaptive milk-derived nanovesicles (MiNVs) for effective oral insulin delivery.
• To overcome intestinal and hepatic barriers for enhanced insulin bioavailability.

Main Methods:

• MiNVs were engineered to bind IgG, facilitating FcRn-mediated transcytosis and avoiding lysosomal degradation.
• MiNVs were designed to release insulin in response to hepatic biothiols.
• Efficacy was evaluated in type 1 diabetic rat and minipig models.

Main Results:

• Oral bioavailability of insulin delivered via MiNVs reached 20.4% in diabetic rats, a 20-fold increase compared to free insulin.
• MiNVs demonstrated effective long-term glycemic control in both rat and minipig models.
• Site-specific adaptability of MiNVs enabled efficient transepithelial transport and targeted release.

Conclusions:

• Site-specific adaptive MiNVs show significant promise for oral insulin administration.
• The developed nanovesicles effectively overcome biological barriers and improve glycemic control.
• This approach enhances insulin bioavailability and offers a potential alternative to injections.