‘Russian doll’ nanoparticles, a new therapeutic approach for tuberculosis

- Research

In an in vitro study researchers have shown how the nanoparticles are more effective than antibiotics alone.  In the future, the nanoparticles will be administered orally as a non-invasive treatment that is much more acceptable to patients.

Tuberculosis is an infectious disease that represents a serious public health problem; according to the WHO, in 2016 10.4 million people got ill with tuberculosis and 1.7 million died. It is essential to advance and develop new tools for diagnosis and treatment and the use of nanoparticles could be a new way to tackle infections caused by Mycobacterium tuberculosis.

To follow this line of research the scientists from the Innovation in Respiratory Infections and Tuberculosis Diagnosis Group at the IGTP worked with a group from the Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, both groups are in the Respiratory Disease Network (CIBERES). They have shown that in vitro the use of nanoparticles of poly-lactic-co-glycolic acid (PLGA) loaded with rifampicin, one of the drugs used in combination treatments for tuberculosis, was more effective than the antibiotic alone.

The research carried out in collaboration with Manuel Arruebo Gordo and Victor Sebastian Cabeza of the CIBER-BBN Group at the University of Zaragoza and the researchers of CIBERES in the Germans Trias i Pujol Research Institute (IGTP): Cristina Prat Aymerich and José Antonio Domínguez-Benítez; together with José Antonio Aínsa Claver of the University of Zaragoza has been published in the journal Nanomedicine.

The researchers have encapsulated rifampicin in nanoparticles, which have then been encapsulated in so-called Russian doll macro-particles which are resistant to the acid pH of the stomach. In this form the micro-particles can be administered orally, which is non-invasive and much better accepted by patients. The particles resist degradation in the stomach and reach the intestine, where they release the nanoparticles of PLGA loaded with the anti-tuberculosis drug and cross the intestinal wall to reach the systemic circulation system and potentially the alveolar macrophages, the cells infected by the pathogen.  Currently, rifampicin is administered orally, however, it is well-known that 25% of the dose administered is destroyed in the stomach. 

The encapsulated drug manages to cross the intestinal wall

In vitro the nanoparticles were able to migrate through an epithelial membrane that mimicked the intestinal wall thereby fulfilling their function in the transport and controlled liberation of the encapsulated drug, which this way avoided contact with the acidic digestive enzymes. "The study is the groundwork for future research based on nanoparticles, aimed at evaluating these nanoparticles with antibiotic in vivo in mice infected with tuberculosis," explains José Dominguez, who together with Cristina Prat, leads the group at the IGTP. 

The authors of the study started their collaboration thanks to the project TARMAC, financed by the Spanish CIBER Network of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), the Respiratory Disease Network (CIBERES) and the Spanish Pulmonology and Thoracic Surgery Society (SEPAR). The project focusses on the development of new tools for the diagnosis and treatment of infectious diseases of the respiratory tract and tuberculosis in particular.

Reference Article

Matryoshka-type gastro-resistant microparticles for the oral treatment of Mycobacterium tuberculosis.  Vanesa Andreu, Ane Larrea, Pablo Rodriguez-Fernandez, Salvador Alfaro, Begoña Gracia, Ainhoa Lucía, Laura Usón, Andromeda-Celeste Gomez, Gracia Mendoza, Alicia Lacoma, Jose Dominguez, Cristina Prat, Victor Sebastian, José Antonio Ainsa & Manuel Arruebo. Future Medicine Published Online: 8 Feb 2019