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Paracellular Delivery of Protein Drugs with Smart EnteroPatho Nanoparticles
Isabela Ramirez-Velez1, Aditya A Namjoshi1, Unyime M Effiong1
1McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.
ACS Nano
|August 3, 2024
Summary
Researchers developed smart nanoparticles that temporarily open pathways in the intestine. This breakthrough enables effective oral delivery of protein drugs, improving patient access and reducing healthcare costs.
Area of Science:
- Biomaterials Science
- Gastroenterology
- Drug Delivery Systems
Background:
- Oral delivery of biologics faces challenges due to the gastrointestinal environment.
- Nanomaterials offer potential for protecting drugs and enabling controlled release in the small intestine.
- Transport across the intestinal mucosa, particularly through the paracellular route, is a key bottleneck for oral protein delivery.
Purpose of the Study:
- To develop a smart nanoparticle system for enhanced oral delivery of biologics.
- To overcome the barrier posed by epithelial tight junctions (TJs) in the small intestine.
- To create a general platform for safe and effective oral administration of protein-based drugs.
Main Methods:
- Engineered "smart" nanoparticles (EnteroPatho NPs) inspired by enteropathogenic bacteria.
- Nanoparticles designed to attach to the epithelial glycocalyx and release TJ modulators.
- pH-responsive release of TJ modulators triggered by the intestinal environment.
- Evaluation of TJ disruption and paracellular protein delivery in vitro/in vivo.
Main Results:
- EnteroPatho NPs successfully attach to the intestinal epithelium.
- The nanoparticles transiently disrupt epithelial tight junctions.
- Demonstrated enhanced paracellular delivery of proteins across the intestinal barrier.
- Established a novel platform for oral biologic drug delivery.
Conclusions:
- Smart nanoparticles can be engineered to modulate intestinal epithelial tight junctions.
- This approach facilitates paracellular transport, overcoming a major hurdle in oral biologic delivery.
- The developed system represents a promising general platform for revolutionizing oral protein drug administration.
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