Monash study uses drug delivery platform that mimics dietary lipid to enhance absorption of widely used opioid replacement therapy
Monash University researchers have harnessed a new drug delivery technology to allow the oral administration of buprenorphine (BUP), a drug used for severe pain management and opioid replacement therapy. At present BUP cannot be administered in a formulation such as a capsule that is swallowed.
The team of researchers, led by Director of the Monash Institute of Pharmaceutical Sciences (MIPS) Professor Chris Porter, have today published preclinical proof-of-concept demonstrating that PureTech’s GlyphTM prodrug technology platform has the ability to increase absorption of BUP up to 20-fold, along with statistically significant increases in lymphatic transport.
GlyphTM is specifically designed to enable the trafficking of small molecule drugs directly into the mesenteric lymphatic system following oral administration.
The paper, published in Frontiers in Pharmacology , is an exciting step towards enabling patients to more conveniently access an oral BUP product to help manage their pain and/or opioid dependence.
“The ability to develop an oral buprenorphine product with good oral absorption properties could address a range of important unmet clinical needs,” said Professor Porter.
“At the moment, the therapeutic potential of buprenorphine is limited by a lack of systemic exposure after the administration of a capsule formulation that can be swallowed. This technology makes that possible. The use of a modified (prodrug) form of the drug that must be processed by the body to release the active form, in combination with a lipid capsule that is not easily dissolved to allow injection, may also help combat diversion of buprenorphine to illicit use.”
GlyphTM generates novel orally dosed prodrugs by reversibly linking small molecule drugs to dietary fat molecules. This linkage is designed to channel the drugs directly into the systemic circulation via the lymphatic system, thereby bypassing first-pass liver metabolism which degrades drugs such as BUP and reduces their systemic exposure.
“The research serves as another proof-of-concept for our GlyphTM platform and illustrates how this novel drug delivery technology can be applied to a range of diseases,” said Joseph Bolen, Ph.D., Chief Scientific Officer of PureTech.
“This latest research reinforces our commitment to leveraging validated biology to accelerate the development of the GlyphTM portfolio to improve the oral bioavailability and/or lymphatic targeting of proven drugs.”
The GlyphTM lymphatic targeting technology was initially created based on intellectual property developed at MIPS (Chris Porter, Natalie Trevaskis, Sifei Han, Luojuan Hu, Tim Quach and Jamie Simpson inventors) and exclusively licensed to PureTech, a Boston based clinical-stage biotherapeutics company, in 2017. MIPS and PureTech scientists have subsequently been working together to further develop the platform. This study was co-led by Dr Sifei Han and the primary authors were Dr Tim Quach and Dr Luojuan Hu.
To read the full article visit: https://www.frontiersin.org/articles/10.3389/fphar.2022.879660/full
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About the Monash Institute of Pharmaceutical Sciences
The Monash Institute of Pharmaceutical Sciences is a dynamic, innovative and ambitious research institute, comprising over 400 scientists engaged in research in drug discovery, design, delivery and use. As part of the world’s top ranked university for Pharmacy and Pharmacology (2022 QS World Rankings by Subject), MIPS’ therapeutic strengths lie in neuroscience and mental health, cardiovascular and metabolic health and global health. The team at MIPS are committed to research translation and have made major contributions to collaborative drug discovery programs that have progressed more than 30 novel drug candidates into clinical development.
About the Glyph™ Technology Platform
Glyph is PureTech's synthetic lymphatic-targeting chemistry platform which is designed to employ the lymphatic system's natural lipid absorption and transport process to enable the oral administration of therapeutics. Glyph reversibly links small molecule drugs to dietary fat molecules, creating a novel prodrug. The linked fat molecule re-routes the drug's normal path to the systemic circulation, bypassing the liver and instead moving from the gut into the lymphatic vessels that normally process dietary fats. PureTech believes this technology has the potential to (1) enable direct modulation of the immune system via drug targets present in mesenteric lymph nodes and (2) provide a broadly applicable means of enhancing the bioavailability of orally administered drugs that would otherwise be reduced by first-pass liver metabolism. PureTech is leveraging validated biology to accelerate the development of a Glyph portfolio, prioritizing highly characterized drugs to enhance with the Glyph technology based on the potential value unlocked in improving their oral bioavailability or lymphatic targeting. PureTech's lead Glyph therapeutic candidate, LYT-300 (oral allopregnanolone), is being evaluated in a Phase 1 study, with results expected in the second half of 2022. PureTech has exclusively licensed the Glyph technology platform, which is based on the pioneering research of Christopher Porter, Ph.D., and his research group at the Monash Institute of Pharmaceutical Sciences at Monash University. The Porter Research Group and collaborators have published research in Frontiers in Pharmacology, Nature Metabolism and the Journal of Controlled Release supporting the Glyph platform's ability to directly target the lymphatic system with a variety of therapies.