What question did this study set out to answer?

This research aims to enhance the oral bioavailability of GLP-1 receptor agonists by utilizing a nanoengineered delivery system.

June 7, 2026

2828-LB: BACH01, a Nanoengineered Platform Enabling Oral Semaglutide with Preclinical Evaluation

Key Points

This research aims to enhance the oral bioavailability of GLP-1 receptor agonists by utilizing a nanoengineered delivery system.
Synthesis and characterization of approximately 600 mesoporous silica nanoparticles.
Screening and encapsulation of semaglutide and related drugs, evaluating release kinetics and cellular uptake.
Pharmacokinetic analysis in small and mid-size animals to assess oral bioavailability.
Lead formulations show 70-200 nm MSN sizes, >90% drug loading, and >60% release over 24 hours.
Achieved significant glucose lowering and body weight reduction in pharmacodynamic studies.
Demonstrated improved oral bioavailability with increased Cmax and AUC in preclinical models.

Abstract

Introduction and Objective: The efficacy of GLP-1RAs is well established, and development has shifted toward improving safety and patient convenience. Oral formulations could enhance treatment adherence but remain limited by poor gastrointestinal stability and low bioavailability of peptide drugs, even with SNAC-based technologies. To overcome these limitations, we developed the NanoLink platform, an innovative mesoporous nanoparticle-based DDS designed to enhance bioavailability, and evaluated the preclinical feasibility of this nano-engineered oral GLP-1RA formulation. Methods: Approximately 600 mesoporous silica nanoparticles (MSNs) across five structural types were synthesized based on a target candidate profile and characterized by TEM and DLS. About 250 candidates were further screened for surface charge and pore size, followed by encapsulation of semaglutide, tirzepatide, and survodutide, release kinetics, cellular uptake, and pharmacokinetic evaluation, leading to the selection of two candidates with the highest oral bioavailability. Results: The two lead formulations showed MSN sizes of 70-200 nm with tunable surface charge, high drug loading (90%), release (~60%/24 h), strong cellular uptake (80%), and stable physicochemical properties under scalable manufacturing conditions. PD studies demonstrated significant glucose lowering and body weight reduction. PK analysis showed significantly improved oral bioavailability compared to control with increased Cmax and AUC in small and mid-size animals, highlighting translational and manufacturing potential. In parallel, preclinical studies, including DRF and ADME, are ongoing. Conclusion: These findings demonstrate that the nano-engineered BACH01 platform enables scalable oral delivery of peptide therapeutics, including GLP-1RAs. The lead candidates have progressed into preclinical development, supporting potential clinical translation of next-generation oral incretin therapies for diabetes, obesity, and related metabolic diseases. Disclosure J. Jung: None.

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