The treatment of lung diseases is most often done with oral medicines such as tablets. However, this type of administration does not always guarantee that the active ingredient reaches sufficient amounts to the lungs, where it needs to act.
The search for a more efficient solution made researchers from USP (University of São Paulo) in Ribeirão Preto, in partnership with the University of Geneva, Switzerland, to develop a new platform that can directly lead to lungs the necessary dose of medicine. The objective, according to Yugo Araújo Martins, responsible for the study and researcher at FCFRP (Faculty of Pharmaceutical Sciences of Ribeirão Preto), is to improve the fight against respiratory infections, making treatment more precise and effective.
The insufficiency of the medication that reaches the lung tissues is explained by the path that the drug makes in the body. Martins states that the medicine passes 1st through the liver, which can change its structure and reduce its effect before reaching the place of infection. As a result, antibiotics and antivirals often reach the lungs at very low concentrations, compromising the effectiveness of treatment.
“One way to circumvent this problem is to extend treatment or increase the dose of the drug. However, this raises the risk of side effects and can overload other organs such as liver and kidneys, especially in longer treatments.”says the scientist. The innovation they created uses lipid nanoparticles that can be administered by nebulization and, as it was designed to imitate the behavior of respiratory viruses, can cross the natural lung defense system.
Lipid nanoparticles are tiny fat -based structures – small that can be up to 1,000 times smaller than the diameter of a human hair. Within them, scientists have put bromexin, a drug already known and used as expectorant that helps dissolve mucus and relieve cough.
When inhaled, these nanoparticles arrive directly to the respiratory system and come into contact with mucus, which is the main barrier of lung protection. At this point, they reproduce the same “path” that viruses use to cross this barrier and reach lung cells – which increases treatment efficiency.
It is an unprecedented approach to increase the effectiveness of the treatment of diseases of the pulmonary respiratory system. “When administered directly to the lungs, nanoparticles need to overcome natural airway defense barriers: the mucus layer [que recobre as células e aprisiona organismos invasores] and the riparian movement of pulmonary cells [promovido por pequenos ‘pelos’ presentes no topo das células que batem ritmicamente e varrem os invasores para fora das vias aéreas]”declares the researcher.
To break this connection with mucus and get rid of riparian movement, respiratory viruses have proteins on their surface. Thus, they are not imprisoned or swept out of the airways. “With these proteins, viruses can ‘roll’ between mucinas, the main molecules that form mucus, and reach cells”says Martins.
Inspired by these characteristics of viruses, lipid nanoparticles containing bromexine also overcome the obstacle of mucus, as they connect and break the bonds with mucinas and, consequently, can enter the pulmonary cells. The researcher believes that imitating virus characteristics in nanometric structures is an intelligent strategy. “This approach helps to better control the behavior of nanoparticles in the body, as well as increasing the accuracy and effectiveness of treatments for various diseases”says.
Control of exacerbated inflammation of viral infections
Upon reaching airway cells, viruses trigger an inflammatory response in the body. It is that they are recognized by the immune system that release cytokines and chemokines – signaling proteins responsible for recruiting defense cells to the site of infection. This process aggravates inflammation and stimulates too much mucus production.
Excessive accumulation of mucus hinders the defense exerted by ciliary beats, making it difficult to eliminate the invading agent. The result of viral infection is the appearance of symptoms such as fever, cough, breathing difficulty or shortness of breath. In more severe cases, inflammation can reach levels so intense that it ends up compromising vital functions and leading to death.
According to the researcher, this mode of operation It is common to all major respiratory viruses, such as influenza virus (influenza), respiratory sintendic virus (ordinary respiratory infections, especially in children and the elderly) and coronaviruses. During the Covid-19 pandemic, this mechanism was evident and had a profound impact on public health. The disease caused the death of more than 716,000 people in Brazil, according to data from the Ministry of Health.
Considering the inflammation process caused by respiratory viruses, the bromexine nanoparticle platform has a 2nd goal: to control excessive inflammation caused by lung infections. In tests performed, the treatment of SARS-COV-2 infected cells with nanoparticles has significantly reduced inflammation and increased the production of a glycoprotein called MUC1, which is present on the surface of the pulmonary cells and has a natural protection role against inflammation.
The new nanotechnological platform can not only cross the lung mucus barrier, but also helps to modulate the response of the immune system in the infection. For researcher Yugo Martins, it is a new and promising strategy to treat respiratory diseases involving inflammation and excess mucus.
The results were obtained in tests with human respiratory epithelium cells infected with the Covid-19 virus, cells that were cultivated in the laboratory to reproduce the real conditions of the respiratory system.
“We created an environment where the top of the cells is in contact with the air and the downstairs in a nutritious liquid”says the researcher, stating that this method makes cells develop similarly to what happens in the human body, producing mucus on their surface.
“The tests simulate more faithful to the reality of the human respiratory tract”declares.
Bromexine nanoparticles cross respiratory defense system to reach infected cells
Platform can serve to convey various drugs
For Martins, the incorporation of active ingredients into nanometric structures, such as those created in their research, is a promising strategy for treating respiratory system diseases such as asthma, tuberculosis and other bacterial and viral infections. Nanoparticles, he says, improve drug solubility, protecting them and collaborating on arrival at sufficient dose pulmonary tissue.
The new platform was designed to “Loading different types of active substances, such as antivirals that combat virus infections, including coronaviruses and influenza virus”.
“In addition, technology can also be adapted to transport antibiotics used to treat bacterial infections and other drugs focused on different respiratory problems. The versatility of the nanotechnological platform paves the way for new more effective and directed therapeutic approaches.”it says.
Although lipids and bromexin (which are part of nanoparticles) are approved by (National Health Surveillance Agency), more tests and investigations should be performed to fully realize the therapeutic potential of lipid nanoparticles in the treatment of respiratory diseases.
With information from.
