Ingestible micro and macro devices for targeted delivery of anti-fibrotic agents to intestinal tissue

Overview

This research program focuses on the development of ingestible micro and macro devices for the targeted delivery of anti-fibrotic agents to fibrotic intestinal tissue. The approach combines established oral drug delivery platforms, including microcontainers and self-unfolding foils, with anti-fibrotic compounds such as Pirfenidone, Sulconazole, and Nintedanib. By enabling site-specific and sustained release in the gut, the technology aims to improve local drug efficacy, enhance bioavailability, and reduce systemic exposure compared to conventional oral formulations.

The work addresses an unmet need in the treatment of intestinal fibrosis, where current systemic therapies often produce off-target effects and suboptimal local concentrations. Site-specific delivery to intestinal cells offers a pathway to more effective treatment with improved safety profiles.

Technical specifications

Key delivery platforms:

• Microcontainers: Small, microfabricated containers designed for oral delivery of small molecules, with demonstrated sustained release and enhanced absorption in vivo compared to powders or liquids.
• Self-unfolding foils: Macroscopic devices that unfold in the gastrointestinal tract to deliver macromolecules and peptides, with preclinical data showing a 12-fold increase in insulin bioavailability in rats and a 4-fold enhancement of nisin delivery in pigs.
• Unidirectional and proximity release coatings: Engineered polymer coatings that protect compounds through the GI tract and enable controlled, localized release at the target site.

Anti-fibrotic integration:

• Evaluation of Pirfenidone, an agent shown to suppress TGF-β and TNF-α signaling and inhibit intestinal fibroblast proliferation.
• Evaluation of Sulconazole in sustained release formulations to elevate local efficacy.
• Evaluation of Nintedanib as an additional candidate for incorporation.
• Coating polymers and a μDISS profiler used to characterize and tune release profiles.

Analytical and validation methods:

• In vitro, ex vivo, and in vivo testing across multiple drug-device combinations.
• CARS microscopy and scanning electron microscope analysis to assess drug incorporation quality.
• Animal studies comparing drug-loaded devices against standard oral medications.

Technology readiness level

The microcontainer and self-unfolding foil platforms have been validated through in vitro, ex vivo, and in vivo studies for oral delivery of diverse small molecules and macromolecules, including insulin and nisin. The current program represents the next step: integrating established anti-fibrotic agents into these validated platforms. Ongoing work includes in vitro screening to identify the optimal drug-device pairing, followed by carefully designed animal studies to benchmark device-enabled delivery against conventional oral medications. The platforms are at a stage ready for collaborative translational development toward intestinal fibrosis applications.