Zwitterionic micelles efficiently deliver oral insulin without opening tight junctions

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Oral protein drug delivery faces challenges with intestinal mucus and epithelial penetration.
• Existing methods lead to low bioavailability and potential safety concerns due to tight junction disruption.

Purpose of the Study:

• To develop a novel zwitterionic micelle platform for enhanced oral protein drug absorption.
• To create a prototype oral insulin formulation with improved bioavailability and safety.

Main Methods:

• Fabrication of a zwitterionic micelle platform with a virus-mimetic surface and betaine side chain.
• Encapsulation of freeze-dried zwitterionic micelle insulin into enteric-coated capsules.
• Evaluation of drug penetration, epithelial absorption, and oral bioavailability.

Main Results:

• The zwitterionic micelle platform facilitated mucus penetration and transporter-mediated epithelial absorption without opening tight junctions.
• The oral insulin formulation achieved a high oral bioavailability of over 40%.
• The formulation demonstrated tunable acting profiles and long-term safety.

Conclusions:

• The developed zwitterionic micelle platform is a promising solution for oral protein drug delivery.
• This technology overcomes key barriers to clinical translation, enabling needle-free administration of protein therapeutics.
• The prototype oral insulin formulation shows significant potential for improving patient treatment and compliance.