BrainDos Formulated Dual GIP/GLP-1 Receptor Agonist Tirzepatide Outperforms Tirzepatide Solution in Preclinical Study

MetP Pharma AG, leveraging the proprietary nose-to-brain drug delivery technology BrainDos in internal and external product development and manufacturing programs, recently announced preclinical data showing that tirzepatide in a BrainDos formulation reduced pro-inflammatory cytokine Il-6 by more than 80% and 2-fold stronger than with aqueous tirzepatide solution. The full effect of the IL-6 reduction with tirzepatide/BrainDos formulation was reached after 4 hours.

MetP Pharma investigated the anti-inflammatory effect of tirzepatide in SH-SY5Y neuroblastoma cell line. The cells were first treated with lipopolysaccharide (LPS) to induce inflammation. After 24 hours exposure to LPS, the cells were treated either with tirzepatide in a BrainDos formulation or aqueous tirzepatide solution (phosphate-buffered saline). The aqueous tirzepatide solution was similar to Lilly’s Mounjaro only slightly differing in the salt composition. The anti-inflammatory effect was determined by measuring interleukine IL-6 reduction.

The tirzepatide/BrainDos formulation reduced IL-6 levels after 4 hours treatment by 87.9% versus a 44.6% reduction with tirzepatide solution. The anti-inflammatory effect of tirzepatide/BrainDos formulation was nearly complete after 4 hours treatment while with tirzepatide solution the effect was more pronounced after 24 hours treatment (44.6% versus 58.6%). The data demonstrate that the BrainDos formulation increases the anti-inflammatory activity by almost 2-fold at 4 hours, and 1.5- fold at 24 hours where it also shows a lasting effect exceeding the effect of the tirzepatide solution. The tirzepatide concentration in both the BrainDos formulation and the aqueous solution was 10nM.

Tirzepatide is a synthetic, dual GIP/GLP-1 receptor agonist that mimics the two hormones naturally produced by the gut and the brain. It is believed that their effect on the central nervous system reduces the feeling of hunger. Due to their charge, these peptide molecules do not pass the blood-brain barrier to a sufficient extent or not at all. BrainDos™ formulation is a potent nose-to-brain drug delivery technology developed to bypasses the blood-brain barrier.

Dr. Claudia Mattern, Chief Scientific Officer at MetP Pharma, said “BrainDos formulated tirzepatide is a potent anti-inflammatory agent outperforming the aqueous tirzepatide solution in reducing IL-6 levels. We believe that the BrainDos technology has the potential to increase the anti-inflammatory effect of weight-loss products such as Wegovy and Mounjaro.”

Recently, MetP Pharma announced preclinical results showing that GLP-1 receptor agonist semaglutide formulated with the BrainDos technology significantly increases drug delivery into cells (1). Chronic brain inflammation is involved in the etiopathology of many neurodegenerative diseases (2) and innovative formulations such as with BrainDos™ technology could have a broad clinical potential far beyond managing obesity.

BrainDos is an intranasal oil-based drug delivery system developed to bypasses the blood-brain barrier (BBB) and allowing precise drug administration. BrainDos consists of a thixotropic oleogel, Silcum, enclosed in a mono-dose applicator (Lecticula). The advanced gel system incorporates the active pharmaceutical ingredient (API) within a lipid-based matrix and exhibits distinctive intranasal drug retention and mucosal adhesion properties thus allowing optimal drug release and exposure to the nasal mucosa. Silcum facilitates the direct entry of drugs to the brain via the olfactory and trigeminal pathways as well as the topical and systemic delivery via the different tissue types in the nasal cavity. Lecticula is a fingernail-sized mono-dose container ensuring easy application and providing high dosing accuracy (± 3%). Its supply chain is secure, there is no risk of shortage and recycling is easy. Lecticula was among the finalists for the 2016 CPhI Pharma Award in the category Excellence in Pharma: Drug Delivery Devices. The filling of the single-dose containers at laboratory, pilot and industrial scale are carried out in specially designed filling machines.

MetP Pharma AG is an independent, specialized pharmaceutical R&D and product development company based in Switzerland. The company has developed BrainDos, an advanced and comprehensively patented nose-to-brain drug delivery system allowing to bypass the blood-brain barrier. The brain targeting effect of BrainDos has been demonstrated through various proof-of-concept studies. BrainDos is a fully developed and flexible technology platform that is significantly reducing the risk of pharmaceutical product development. The company’s internal product development program includes intranasal products for the indications concussion, insomnia, attention deficit hyperactivity disorder (ADHD), multiple sclerosis (MS) and hypogonadism.

MetP also provides pharmaceutical development services based on its proprietary and worldwide patented intranasal BrainDos delivery technology. The company’s research has been published in 65 peer-reviewed journals and a robust intellectual property portfolio exist in many countries until 2037/2039.