A pill instead of a needle
Therapeutic drugs and vaccines based on nucleic acids, including the COVID-19 vaccine, are available only in the form of injectable drugs, since these molecules cannot survive passage through the gastrointestinal tract. Injectable drugs often lead to low adherence of patients to treatment, as they cause discomfort and require a qualified specialist for administration.
Researchers at the Massachusetts Institute of Technology have developed a capsule that can attach to the gastric mucosa and releases an RNA vaccine. This approach can also be used to deliver other RNA or DNA-based drugs directly into the digestive tract, which can facilitate the treatment of gastrointestinal disorders. Researchers have shown that they can use the capsule they developed to deliver up to 150 micrograms of RNA into the stomach of pigs – more than the amount used in mRNA vaccines against Covid.
In 2019, the group developed a capsule that can hold dry contents, in 2021 they created a capsule to deliver large molecules, such as monoclonal antibodies, in liquid form. Now the researchers have tried using the capsule to deliver nucleic acids, which are also large molecules.
Nucleic acids are susceptible to degradation when ingested, so they must be carried by protective particles. For this study, the MIT team used a new type of polymer nanoparticles made of poly (beta-aminoesters). Previous work has shown that branched versions of these polymers are more effective in protecting nucleic acids when entering cells, as opposed to linear ones, and the joint use of both of these polymers is even more effective. This will reduce the total number of nanoparticles that need to be injected.
To test the particles, the researchers first injected them into the stomachs of mice without using a capsule for delivery. The RNA contained in them encodes a reporter protein that can be detected if it successfully integrates into cells. The researchers found a reporter protein in the stomach as well as the liver of mice, suggesting that the RNA got into the cells of other organs of the body, and then transferred to the liver, which filters the blood.
The researchers then sublimated the complexes of RNA nanoparticles and packed them into capsules for drug delivery. They were able to load about 50 micrograms of mRNA into one capsule and injected three capsules into the stomach of pigs – a total of 150 micrograms of mRNA. This is more than the amount of mRNA in currently used injectable Covid vaccines containing 30 to 100 micrograms of mRNA. Reporter protein was successfully produced by stomach cells, but was absent in other organs. In future work, the researchers hope to increase the absorption of RNA by other organs by changing the composition of nanoparticles or introducing large doses. However, as the authors hope, a strong immune response can also be triggered when delivered only to the stomach. There are many immune cells in the gastrointestinal tract, and their stimulation is a well-known way to create an immune response.
The researchers plan to study whether they can generate a systemic immune response, including activation of B and T cells, by delivering mRNA vaccines using a new capsule. This approach can also be used to create new treatments for gastrointestinal diseases that are difficult to treat with injections.
Article by Abramson et al. Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections is published in the journal Matter.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on MIT materials: Making RNA vaccines easier to swallow.