The research team invented an oral injection needle that is non-invasive and painless to achieve better efficacy

When you are sick, if there are two treatment options, medicine and injection, which one are you more inclined to choose? At present, oral medication has been iterated continuously due to technological innovations, hoping to free patients from the pain of injection medication by increasing the amount of drug loaded and optimizing the dynamics of drug metabolism
.

However, in some patient groups suffering from diabetes, Crohn's disease and other diseases, because oral methods cannot provide large-dose, fast-acting drugs, the efficacy of injection is significantly better than oral

Recently, a research team from the Massachusetts Institute of Technology in the United States published a research article titled "Oral delivery ofsystemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors" in "Nature Biotechnology".
They developed a research article called "L-SOMA".
"Injection needle capsule, this small pill has been given a new drive and transmission system, which can be loaded with small molecule drugs, but also large molecule drugs such as monoclonal antibodies, and the drug load has been doubled
.

What's more noteworthy is that the pill can reach a maximum plasma concentration of the drug similar to the standard of subcutaneous injection within 30 minutes after administration, and can reach an absolute bioavailability of 80% within a few hours

The L-SOMA capsule designed in this study, with a diameter of 12 mm and a height of 15 mm, can be injected into the submucosa of the stomach to systematically deliver liquid drugs
.

The researchers imitated the geometry of the tortoise in the design and developed a weighted bottom and a hollow shell, which allows the capsule to be repositioned on the stomach wall even if it is disturbed

In order to deliver the drug, L-SOMA uses a staged, sequence-controlled multi-spring drive system.
This system is located above the capsule and is equipped with three springs.
One of the springs helps eject the injection needle so that it can be inserted under the gastric mucosa.
, There are also two springs to help the medicine flow into the injection needle
.

In order to allow the spring to work at the right time, the researchers used soluble particles to fix the spring.

L-SOMA capsule design drawing

After determining how the capsule works, the researchers conducted experiments in isolated porcine gastric tissue to study the optimal needle penetration depth for targeting the submucosa of the stomach
.

The test results show that for the needle injection depths of 3mm and 4mm, the drug dose is sometimes delivered to the mucosa instead of the submucosa.

Next, the researchers conducted large animal tests on L-SOMA capsules to verify its effectiveness and safety
.

They used live pigs as the research object and injected four drugs into L-SOMA capsules: 0.

The test results showed that the pig stomach showed faster pharmacokinetics within 15 minutes of administration
.

Within 15 minutes after L-SOMA completed the administration of insulin, inactivated GLP-1 analogs or epinephrine, the researchers observed the presence of these three drugs in the plasma; and within 1 hour of the administration of monoclonal antibodies, The researchers observed the presence of the drug in the serum; the half-life of the drug injected into the body through L-SOMA was the same as that of subcutaneous injection within at least 3 days after administration

Subsequently, the researchers performed the bioavailability of L-SOMA capsules and subcutaneous or intramuscular injections
.

The results of the study showed that insulin administered via L-SOMA showed a bioavailability of 51%±16% during a 2-hour sampling period, compared to 57%±8% of insulin injected subcutaneously; The bioavailability of L-SOMA's GLP-1 analog is 103%±42%, while the bioavailability of subcutaneously injected GLP-1 analog is 78%±4%, which shows that the administration of L-SOMA capsules can achieve The bioavailability is similar to that of subcutaneous injection.

After the administration, the researchers monitored the animals for 1 week or euthanized the animals to evaluate the safety and feasibility of multi-day administration
.
The results showed that after the administration, all animals maintained normal behaviors and eating patterns, and no bloodstains were observed in the feces
.
No abnormalities were found in the H&E stained histological samples collected from the injection site within 2 hours after administration.
This result shows the safety of L-SOMA capsules
.

In view of the feasibility, the researchers took L-SOMA capsules and another capsule different from L-SOMA to awake living dogs.
These capsules do not contain the drug formula, but the size and size of the two capsules are different.
The density distribution is similar
.
The results showed that all animals swallowed the capsules effortlessly.
Through radiographic monitoring, the researchers observed the process of the capsule reaching the stomach, being activated, and then completely passing through the gastrointestinal tract as expected
.

In general, the design of the L-SOMA capsule is completely safe and feasible in the trial
.
It not only facilitates rapid pharmacokinetic absorption within a few minutes after administration, but also has a drug loading capacity of up to 4 mg, which allows the capsule to fuse with drugs that were previously unable to be taken orally to achieve patient Achieve better curative effect in a non-invasive and painless environment
.
At present, this test is still in its infancy
.

Note: The original text has been deleted

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