Combatting the Opioid Crisis with Liposomal Adjuvant Systems

Posted on April 05, 2022


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Headlines across the globe have largely been dominated by the COVID-19 pandemic for the last two-plus years – and rightly so. But infectious diseases such as COVID-19 are not the only public health crises that we face. Heart disease, cancer, and diabetes affect millions of lives every day, and we hear about the research being done to combat them regularly. In this research spotlight, let’s take a look at a public health crisis that we garners less attention – the opioid addiction crisis.

The days of believing that addiction is simply a lack of willpower are in the past. Research has proven that substance abuse alters brain chemistry and the circuits related to pleasure and reward. Once these changes have been induced, they last much longer than the sensation provided by the opioid. Opioids – heroin, synthetic fentanyl, and prescription pain killers – not only take a toll on those that become addicted and abuse them, but also on the economy. It is estimated that the opioid crisis puts an annual burden of more than $75 billion on the U.S. economy alone (NIH.gov, 2020). So, addressing this health crisis through science and research is just as important as the others that we hear about every day.


Using Vaccines to Fight Heroin and Fentanyl Addiction

Current methods for treating opioid overdose are limited. They need to be administered quickly after opioid overdose, and they typically do not work well if fentanyl is involved. Vaccines aren’t just for the flu or COVID-19, they have been targeted as a therapeutic agent to combat the opioid crisis as well. Research being done at the Walter Reed Army Institute of Research has been investigating a vaccine that could attenuate heroin and fentanyl effects in those that receive it.

The vaccine being investigated is composed of a molecule that is structurally similar to the opioid that it targets. This molecule is conjugated to an immunogenic carrier protein and formulated with a liposomal adjuvant system to further stimulate the immune response. Once injected, this system will induce the production of antibodies that target and trap opioids found in the blood which reduces any physiological effects that might be experienced by preventing their access to the brain. Antibodies that trap opioids are highly selective, so a vaccine targeting more than one type of opioid would need to have a combination of vaccines to successfully trap them all. A vaccine of this nature is referred to as polyvalent and is not uncommon when targeting multiple protein antigens. Targeting multiple small molecules with polyvalent vaccines on the other hand, is relatively unexplored.

Avanti’s Lipids Fighting Heroin and Fentanyl Addiction

The liposomal adjuvant system being used to administer opioid haptens is made of Avanti lipid products! Army Liposome Formulation 43 (ALF43) is a formulation consisting of 43% cholesterol and 57% phospholipids. The phospholipid portion of the formulation was composed of DMPC, DMPG, and 3D-PHAD with an adjuvant to phospholipid ratio of 1:8.8 (Singh, et. al., 2020). The liposomal adjuvant encapsulated haptens were then adsorbed to Alhydrogel. So, how did the polyvalent vaccine work?

These vaccines were studied in mice and the antibody affinity was measured at various time points after administration of the vaccine. A further step was taken to study the cross-reactivity of this vaccine with some common opioid receptor agonists such as methadone and buprenorphine, and antagonists like naloxone. The study found the polyvalent vaccine to be a promising method for treatment of heroin and fentanyl usage! Injection of the vaccine in mice induced a high level of anti-hapten Immunoglobulin G (IgG) antibody titers. The IgG was also found to strongly bind to heroin, morphine, and fentanyl at nanomolar affinity. And to top it off, the vaccine proved to protect the mice from thermal anti-nociception induced by heroin, fentanyl, and even with heroin + 9% fentanyl. Cross-reactivity of the polyvalent vaccine with opiod receptor agonists/antagonists was found to be very little (less than six percent).

This treatment method has a long road ahead before it can be tested in humans, but this proof-of-concept is promising nonetheless! It is exciting to see our lipids being studied and used to protect people from infectious diseases, cancer, diabetes, and for opioid addiction. If you are interested in formulating your own liposomal adjuvant systems, check out the products used in ALF43 (DMPC, DMPG, cholesterol, and 3D-PHAD). If you would like some help formulating this liposomal adjuvant system or need help altering it for your specific therapeutic delivery needs, contact our Formulations team today! People do amazing things with our lipids. We can’t wait to see what you will do!

Click to read the full research article “Bivalent Conjugate Vaccine Induces Dual Immunogenic Response That Attenuates Heroin and Fentanyl Effects in Mice

References:

Opioid Addiction. (2020, Feb. 11) National Institutes of Health. https://www.nih.gov/about-nih/what-we-do/nih-turning-discovery-into-health/opioid-addiction

Singh, P., Matyas, G., Anderson, A., Beck, Z. Biophysical Characterization of Polydisperse Liposomal Adjuvant Formulations. (2020). Elsevier. https://www.sciencedirect.com/science/article/abs/pii/S0006291X20310937