Lexaria Bioscience Corp. has announced promising results from a preclinical biodistribution study showing that its DehydraTECH drug delivery technology significantly enhances semaglutide distribution to the brain compared to conventional oral formulations. The findings could have important implications for improving the safety and efficacy profile of GLP-1 diabetes and obesity treatments.
Enhanced Brain Penetration Across All Doses
The study's most significant finding was that Lexaria's DehydraTECH-processed fluorescently tagged semaglutide (FTS) demonstrated consistently higher brain biodistribution across all tested doses compared to a Rybelsus equivalent composition and study controls. Remarkably, the 5mg DehydraTECH-FTS formulation achieved higher brain semaglutide fluorescent signal intensity than the 15mg Rybelsus equivalent composition, suggesting a three-fold improvement in delivery efficiency.
When researchers sectioned brain tissue into 2-3mm sagittal slices for detailed analysis, they found that all three DehydraTECH doses tested displayed fluorescence above naive and vehicle control groups. In contrast, only the highest dosage (15mg/kg) of the Rybelsus equivalent composition surpassed the control groups.
Targeting Critical Brain Regions
The enhanced distribution was particularly notable in brain regions known to be crucial for semaglutide's therapeutic effects. These included the brainstem, which has direct semaglutide interaction sites; the paraventricular nucleus of the hypothalamus, involved in energy homeostasis; and circumventricular organs that lack a blood-brain barrier, such as the area postrema, subfornical organ, and median eminence.
"Lexaria has repeatedly evidenced higher brain levels upon gross necropsy in rodent studies with other DehydraTECH-processed active ingredients in the past that demonstrated superior safety and efficacy over controls," said John Docherty, Lexaria President and CSO. "We are delighted to now see early evidence of this through more detailed fluorescent imaging with DehydraTECH-semaglutide which may, in turn, help to explain the performance benefits in safety and efficacy we have witnessed in our related human clinical testing to-date."
Clinical Implications for GLP-1 Therapy
The enhanced brain biodistribution could address a key challenge in current GLP-1 therapy. Semaglutide regulates body weight through direct and indirect activation of GLP-1 receptors on several independent brain nuclei, affecting neuronal pathways involved in food intake, reward, and energy expenditure. Studies in rodents have suggested that GLP-1 analogs can act on the brain to suppress appetite without causing nausea, which is among the most common side effects of current GLP-1 therapies.
The company's discovery of enhanced semaglutide brain biodistribution using DehydraTECH technology could potentially impact both the safety and efficacy performance of current and next-generation GLP-1 drugs by enabling therapeutic effects while minimizing gastrointestinal side effects.
Study Design and Methodology
The preclinical pilot study evaluated biodistribution of oral semaglutide formulated using either DehydraTECH or a Rybelsus equivalent composition in 25 male Sprague Dawley rats. The Rybelsus equivalent composition was created by Lexaria for research purposes, containing ingredients believed to be in the correct proportions used in Novo Nordisk's commercially available product, but without DehydraTECH processing.
Researchers used single oral gavage dosing followed by imaging at multiple time points up to 24 hours post-dosing. The semaglutide was tagged with a cyanine 7 fluorophore, chosen for its near-infrared excitation wavelength that allows deeper tissue penetration and minimal tissue autofluorescence. Various tissues known to express GLP-1 receptors were examined, including brain, pancreas, lung, kidney, liver, and heart.
The study was performed by an independent animal research facility specialized in pharmacokinetic evaluations. Due to the limited size of this pilot study, conclusions were made qualitatively based on visual comparisons of images and graphs, with no statistical analyses performed.
Supporting Previous Clinical Evidence
These preclinical findings align with results from Lexaria's previous human pilot studies GLP-1-H24-1 and GLP-1-H24-2, which showed marked safety and efficacy improvements with DehydraTECH-processed Rybelsus compared to Rybelsus alone. The company suggests that complementary biodistribution benefits might be achieved by combining DehydraTECH semaglutide processing with Rybelsus excipients.
Lexaria considers these early-stage results highly encouraging and supportive of both additional research and industry partnerships designed to produce safer and more effective GLP-1 drugs. The company's DehydraTECH platform technology, protected by 50 granted patents with additional patents pending worldwide, has repeatedly demonstrated the ability to increase bio-absorption, reduce side effects, and deliver drugs more effectively across the blood-brain barrier.
