Psychotropic drugs interaction with the lipid nanoparticle of COVID-19 mRNA therapeutics

Abstract

The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions. The COVID-19 mRNA vaccines are of particular interest as they form the vanguard of a range of other mRNA therapeutics that are currently in the development pipeline, focusing both on infectious diseases as well as oncological applications. The Vaccine Adverse Event Reporting System (VAERS) has gained additional attention during the COVID-19 pandemic, specifically regarding the rollout of mRNA therapeutics. However, for VAERS, absence of a reporting platform for drug-vaccine interactions left these events poorly defined. For example, chemotherapy, anticonvulsants, and antimalarials were documented to interfere with the mRNA vaccines, but much less is known about the other drugs that could interact with these therapeutics, causing adverse events or decreased efficacy. In addition, SARS-CoV-2 exploitation of host cytochrome P450 enzymes, reported in COVID-19 critical illness, highlights viral interference with drug metabolism. For example, patients with severe psychiatric illness (SPI) in treatment with clozapine often displayed elevated drug levels, emphasizing drug-vaccine interaction.

Effectiveness of AstraZeneca vaccine against SARS-CoV-2 (ChAdox1-S) in reducing in-hospital mortality in individuals with COVID-19 and schizophrenia: A retrospective cohort study

“… 21 For example, it was previously reported that individuals with severe psychiatric illness have lower counts of regulatory T cells and increased number of natural killer cells. 22 In addition, the anti-inflammatory and immunosuppressant action of psychotropic drugs may lower immune reactivity necessary for adequate vaccine response. 22 …”

“… 22 In addition, the anti-inflammatory and immunosuppressant action of psychotropic drugs may lower immune reactivity necessary for adequate vaccine response. 22 …”

The MSH3 Gene From A Neuropsychiatrist’s Perspective

“…Indeed, we envision a near future when micro or nano grams of LNP-attached psychotropic drugs could be delivered to intra neuronal targets, averting systemic adverse effects. However, for that to happen, the LNP may need to be redesigned as some of the currently utilized lipids may interfere with the psychotropic drugs as we recently documented [49].…”

Identification of film-based formulations that move mRNA lipid nanoparticles out of the freezer

“…In the endosome, ionizable lipids revert to their original positively charged state where they interact with anionic phospholipids to disrupt the endosomal membrane and facilitate release of intact mRNA-containing micelles into the cytoplasm. 6 , 7 Neutral phospholipids and cholesterol are responsible for maintaining an organized lipid shell. Helper lipids such as distearoylphosphatidylcholine (DSPC) also contribute to endosomal escape by interacting with the endosomal membrane.…”