Lexaria article sent out by email today
Lexaria is investigating applications of its patented DehydraTECH technology for more effective delivery of existing antiviral drugs. Although these drugs are in a different class from those we've traditionally worked with, the underlying concept is identical to everything Lexaria has accomplished in recent years: use our own proven technology to deliver drugs more effectively. If DehydraTECH can deliver antiviral drugs with higher absorption rates, we can do our part to make the world a better place.
Solving the Bioavailability Problem
Why this is Critical for Oral Antivirals against COVID-19 and other Infectious Diseases
Infectious Disease Surrounds Us
Infectious diseases are disorders caused by invading microorganisms or other agents such as bacteria, viruses, fungi or parasites. Many microorganisms live in our bodies that are normally harmless or even helpful. However, in some cases, they can cause illness or even death and they can be widely transmitted via insects and animals, food and water, or passed from person to person.
Viruses and bacteria cause the most common infectious diseases in the world today (Christiansen., 2018). Vaccines can offer protection against contracting viral and bacterial infections, whereas antiviral drugs and antibiotics respectively are required as treatments to combat disease if vaccination or other protective measures are inadequate or are not available.
Absent effective vaccines or therapeutics, infections can have widespread effects on the human body. COVID-19 caused by infection with the novel coronavirus SARS-CoV-2 is a startling example of this, whereby it is generally regarded as a respiratory infection but is also known to have potentially serious effects upon other organs as well as the circulatory system. SARS-CoV-2 is known to enter human cells by binding a receptor protein found throughout the human body known as the ACE2 receptor, following which it can multiply and spread wildly. Upon doing so, the human immune system response can actually be overly powerful and lead to death in extreme cases, whereby high levels of immune cells called macrophages and neutrophils, as well as immune chemicals called cytokines and chemokines can accumulate in the cells which, in turn, can fatally impede normal bodily function. In the lung and airway tissues, this can manifest as acute respiratory distress syndrome (ARDS) and severe pneumonia due to the accumulation of immune cell rich fluids in the lungs. In the circulatory system, this can also manifest as small or large blood clots which, in turn, can cause multiple organ failure situations almost anywhere in the body, although researchers are still endeavoring to understand the precise relationship between the overactive innate human immune response and formation of these potentially fatal blood clot events.
Medicines for Treating COVID-19 and Other Infectious Diseases
The world was caught by surprise upon the emergence of the novel coronavirus, in response to which scientists worldwide began a global effort to determine if any existing antiviral drugs for other conditions may be able to combat it. These so called “repurposed” drugs that have shown promise have included drugs like remdesivir, interferon beta-1b, lopinavir, ritonavir and ribavirin among others, evaluated alone and in combination treatment regimens (Lu et al.,2020). Most of the antiviral drugs currently available are used to treat infections caused by HIV, herpes viruses, hepatitis B and C viruses, and influenza A and B viruses. They are generally designed to act by arresting the viral integration and replication cycle at the cellular level at various stages in order to prevent entry and widespread proliferation throughout the body, thereby reducing a patient’s overall viral load. Scientists are also actively investigating ways to develop new antiviral drugs tailored to blocking these aspects of SARS-CoV-2 virus infection specifically.
The Oral Bioavailability Problem
While a host of antiviral drugs exist or are under development today, many of them are hindered by poor water solubility which, in turn, results in their poor absorption and uptake by the body if taken orally. The reason for this is because the human gastrointestinal system is designed to absorb nutrients and other ingested compounds that are primarily water soluble rather than fat soluble or “lipophilic”. And, compounding this problem, the human gastrointestinal system is further designed to channel most compounds it absorbs through the liver for detoxification prior to entry into the bloodstream, which functions as another absorption impediment for many antiviral drugs if taken orally. In concert, these physiological limitations can result in so called low oral bioavailability for many antiviral drugs, interfering with how well they can reach the bloodstream after ingestion and, in turn, frequently limiting their overall therapeutic effectiveness (Ford et al., 2020).
To attempt to overcome this, oral antiviral medications often have to be given at high doses which can result in a variety of unwanted side effects including diarrhea, headache, nausea, vomiting, stomach upset, drowsiness, dizziness, vision changes, difficulty breathing and other bodily dysfunctions. Alternatively, in some cases it is necessary to administer antiviral medications by way of needle injection for easier access to the bloodstream circumventing the gastrointestinal absorption limitations. Remdesivir, as mentioned above, is one such example of an antiviral medication administered by injection instead of orally for this reason. However, injectable administration requires involvement of a medical practitioner which may not be easily accessible for the masses, usually increases cost of a medicine and often means that the product format isn’t as stable or requires special storage and handling considerations relative to oral medications.
Introducing DehydraTECH™ – Effective Oral Delivery for Poorly Water Soluble Drugs
DehydraTECH is a patented formulation processing technology developed by Lexaria Bioscience Corp. and licensed to its wholly owned subsidiary Lexaria Pharmaceutical Corp. that has been shown to enhance the performance of lipophilic drugs in oral ingestible products by way of increased rate and extent of intestinal bioabsorption and delivery to target tissues. DehydraTECH is believed to accomplish this by effecting a temporary molecular association between a given drug compound of interest and certain long chain triglyceride (LCT) ingestible oils, such as oleic acid rich sunflower oil, so that the physiological absorption benefits of the LCTs are conferred upon the drug compound. In particular, LCTs are known to be absorbed intestinally by a specialized process in concert with biliary excretions in the human gut that results in their rapid channeling into the bloodstream bypassing metabolism by the liver (Zgair et al., 2016; Reddy and Murthy, 2002). In short, DehydraTECH is thought to enable delivery of lipophilic drugs in effect as “payload” compounds in tow with the LCTs that power DehydraTECH formulations.
DehydraTECH formulations have been prepared with a range of lipophilic beneficial molecules of interest and administered orally to animals and humans to investigate their absorption and pharmacological performance enhancing attributes. Active ingredients formulated and/or evaluated to-date with the DehydraTECH technology have included cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol, terpenoids, nicotine polacrilex, ibuprofen, geraniol, catachin and sildenafil citrate. For example, oral DehydraTECH formulations of CBD have been studied demonstrating as high as an 811% increase in CBD blood perfusion in animals overall and as high as a 317% increase within the first 30 minutes of administration in human volunteers without any safety or tolerability concerns (Patrician et al., 2019).
DehydraTECH™ Antiviral Research Underway
Based on Lexaria’s success to date in developing and commercializing DehydraTECH oral product formats for other lipophilic drug compounds, it is actively investigating its prospective utility to improve the bioavailability of antiviral drug candidates. Studies underway and/or in the planning stages include pilot testing in human volunteers to determine the rate and extent of bioavailability enhancement for certain repurposed antiviral medications upon oral administration, as well as testing to follow this that will evaluate if this translates into increased effectiveness against SARS-CoV-2 and/or other infections in appropriate laboratory and animal models. If successful, the Company intends to make its DehydraTECH technology available to prospective research partners throughout the world looking to maximize the effectiveness of their own drug investigations with a view to enabling development of safe, effective and readily commercially accessible/viable oral antiviral medications against COVID-19 and other infectious diseases, whether for repurposed existing drugs and/or for new emerging drug candidates. Furthermore, as noted above, Lexaria has previously demonstrated utility of its DehydraTECH technology for formulating drugs with known anti-inflammatory properties like nonsteroidal anti-inflammatory drugs and CBD. Therefore, the Company also envisions its technology being useful for the development of multipronged therapeutic strategies for COVID-19 and other infectious diseases where reduction in viral load together with mitigation of the human innate immunological inflammatory response may be necessary in concert to improve therapeutic outcomes for patients.
Conclusion
In summary, Lexaria believes that its DehydraTECH technology has the potential to significantly increase bioavailability for potentially many oral antiviral medications. This, in turn, is expected to make oral antiviral drugs work more effectively for better therapeutic outcomes and at lower doses than are otherwise necessary in order to minimize unwanted side effects. Furthermore, this may also make the oral route of administration a viable alternative to injection for certain antiviral medications which could lead to better cost effectiveness and wider availability without the added complexity of formulating and administering injectable preparations. Finally, Lexaria believes that its DehydraTECH technology has the added potential to help treat serious viral conditions like COVID-19 by enabling improved anti-inflammatory drug delivery and effectiveness, which may prove to be of critical importance to decrease disease severity together with reducing viral load with antiviral therapies.
REFERENCES
1. Christiansen J. (2018) Infections by the Numbers. Sci. Amer. 318(5), 48-49
2. Ford N, Vitoria M, Rangaraj A, Norris SL, Calmy A, Doherty M. (2020) Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID-19: initial assessment. J Int AIDS Soc. Apr;23(4):e25489.
3. Lu H: Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020 Jan 28. doi: 10.5582/bst.2020.01020
4. Patrician A, Versic-Bratincevic M, Mijacika T, Banic, I, Marendic M, Sutlovic D, Dujic Z, Ainslie PN. (2019) Examination of a new delivery approach for oral cannabidiol in healthy subjects: a randomized, double-blinded, placebo-controlled pharmacokinetics study. Advances in Therapy. 36 (11), 3196-3210.
5. Reddy LHV, Murphy RSR. (2002) Lymphatic transport of orally administered drugs. Indian J Exp Biol, 40, 1097-1109
6. Zgair A, Wong JCM, Lee JB, Mistry J, Sivak O, Wasan KM, Hennig IM, Barrett DA, Constantinescu CS, Fischer PM, Gershkovich P. (2016) Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. Am J Transl Res. 8(8): 3448–3459
Forward-Looking Statements
Statements in this release concerning Lexaria’s future expectations and plans, including, without limitation, the use of proceeds from the offering, financial needs of the Company and potential uplisting onto a national stock exchange may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place undue reliance on these forward-looking statements, which include words such as “could,” “believe,” “anticipate,” “intend,” “estimate,” “expect,” “may,” “continue,” “predict,” “potential,” “project” or similar terms, variations of such terms or the negative of those terms. Although Lexaria believes that the expectations reflected in the forward-looking statements are reasonable, Lexaria cannot guarantee such outcomes. Lexaria may not realize its expectations, and its beliefs may not prove correct. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described in the section entitled “Risk Factors” in Lexaria’s most recent Annual Report on Form 10-K and Lexaria’s other filings made with the SEC. All such statements speak only as of the date made. Consequently, forward-looking statements should be regarded solely as Lexaria’s current plans, estimates, and beliefs. Lexaria cannot guarantee future results, events, levels of activity, performance or achievements. Lexaria does not undertake, and specifically declines, any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law.
Lexaria Bioscience Corp.
#100-740 McCurdy Road
Kelowna, BC V1X 2P7.
www.lexariabioscience.com
Copyright © 2019, Lexaria Bioscience Corp, All rights reserved.
unsubscribe from this list update subscription preferences
AI
