A nasally injected brain preparation can help treat depression for 20 minutes

Imagine feeling depressed. And fix it with nasal spray.

Something similar could happen in the near future thanks to researchers in Japan who have significantly strengthened an effectively injected nasal antidepressant drug for the brain, according to a recent study. published in Controlled Release Magazine.

Recent research presents a new concept for drug delivery systems, describing a technological solution that could have far-reaching implications for neuropharmaceutical research.

But most importantly, the effects are observed to take effect within 20 minutes. And that opens the door to futuristic methods of brain delivery, including nanobiotechnology, in addition to genetic engineering (for adults, of course).

Overcoming the challenges of antidepressant brain drugs

Delivering drugs to your brain to treat disease has historically remained a challenging horizon for scientists, thanks to persistent obstacles such as systemic absorption, rapid drug degradation, axonal transport, and the relatively invasive extremes often required by conventional techniques. Thus, researchers in Japan have tried to increase the supply of drugs to the brain to elevate this method and make it as effective as other delivery techniques. This was done by adding sequences to improve cell permeability, in addition to the ability to avoid degradation, to an antidepressant drug called glucagon-like peptide 2. But this did not become easy.

Modern methods of injecting the drug directly into the brain, known as intracerebroventricular (ICV) administration, are understandably invasive. Alternative methods, including intranasal administration, face problems that reduce their value, including ineffective cell permeability. And even when the drug reaches the brain and penetrates the neurons, their ability to act on the brain is often reduced due to the rapid deterioration of the drug’s effectiveness, in addition to the slow transport of axons.

Diagram showing how the nasally injected antidepressant works. Source: Tokyo University of Science

The modified drug showed efficacy within 20 minutes

The research team is a team of Japanese researchers led by Professor Chikamasa Yamashita of the University of Tokyo Science. Combining efforts and resources, the team eventually succeeded in implementing glucagon-like peptide-2 (GLP-2) in a mouse model of depression. Modifications made to the drug allow it to move faster without degrading too much, while showing the same therapeutic effects as ICV, according to a recent study. “Although there have been more than 20 years of phenomenal IDD research, I wondered why it has not been used in practice. Then I realized that most IDD research focused on drug delivery through the olfactory epithelium, which is 2% of the human nasal mucosa, “said Professor Yamashita in a blog post from Tokyo University of Science.” Alternatively, my team focuses on the central delivery of drugs through the remaining 98% of such mucosa – respiratory epithelium, in particular through the trigeminal nerve. “

The team worked with GLP-2, a known neuropeptide exhibit therapeutic effects, even in treatment-resistant depression. Because many drugs that enter the body quickly lose their effectiveness from endosomal degradation in living cells, the Japanese team chose to add a peptide-derived sequence to GLP-2, known as the Penetration Acceleration Sequence (PAS). This sequence allows the drug to avoid degradation over a longer period of time. The researchers also improved the drug’s ability to “pierce” the respiratory epithelium and other surfaces in the body, the penetration of which can reduce effectiveness. And they found that the modified drug was therapeutically effective in a murine model of depression within 20 minutes, comparable to ICV administration. While a revolutionary achievement in nasally injected antidepressants, it is also a step towards the future of nanobiotechnology, and genetic engineering; two nascent fields with seemingly unlimited applications.

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