A pH-Triggered Self-Unpacking Capsule Containing Zwitterionic Hydrogel-Coated MOF Nanoparticles for Efficient Oral...

Area of Science:

• Biomaterials Science
• Drug Delivery
• Endocrinology

Background:

• Oral peptide/protein delivery faces challenges from the gastrointestinal environment and intestinal epithelium, resulting in low bioavailability.
• Subcutaneous injection remains the standard for peptide/protein therapeutics, despite patient inconvenience.
• Developing oral delivery systems is crucial for improving patient compliance and therapeutic outcomes.

Purpose of the Study:

• To engineer a pH-triggered self-unpacking capsule for oral delivery of exendin-4.
• To enhance exendin-4 protection against gastrointestinal degradation and promote intestinal penetration.
• To evaluate the efficacy of oral exendin-4 delivery in a diabetes rat model.

Main Methods:

• Fabrication of pH-triggered self-unpacking capsules encapsulating zwitterionic hydrogel-coated metal-organic framework (MOF) nanoparticles.
• Loading of exendin-4 into MOF nanoparticles with high capacity.
• Assessment of mucus permeation and epithelial cell internalization by zwitterionic hydrogel-coated nanoparticles.
• Oral administration of exendin-4-loaded nanoparticles in a diabetes rat model.
• Measurement of plasma exendin-4 levels, insulin secretion, and blood glucose levels.

Main Results:

• The engineered capsules demonstrated gastro-resistance and pH-triggered self-unpacking in the intestinal environment, releasing nanoparticles.
• Zwitterionic hydrogel coating facilitated mucus permeation and epithelial cell internalization of nanoparticles.
• Oral administration resulted in enhanced plasma exendin-4 levels for over 8 hours.
• Significant increases in endogenous insulin secretion and a notable hypoglycemic effect were observed.
• A relative pharmacological availability of 17.3% was achieved for oral exendin-4.

Conclusions:

• The pH-triggered self-unpacking capsule system effectively protects exendin-4 from gastrointestinal degradation and enhances its oral bioavailability.
• This novel oral delivery strategy shows significant potential for facile and convenient daily diabetes management.
• The developed system offers a promising alternative to subcutaneous injections for peptide-based diabetes therapies.