Priorities to achieve the WHO goal of ending tuberculosis (TB) epidemic by 2030 include new drug treatments to simplify and shorter conventional drug regimens. TB is caused by Mycobacterium tuberculosis residing and surviving inside alveolar macrophages (AM). Considering that 75-80% of cases of infection remain localized in the lungs, the easiest and most successful therapy could involve the inhalation route offering benefits in terms of patient’s autonomy and compliance, by-passing hepatic metabolism, reducing dose amount, dose frequency, and treatment duration, thus minimising the risk of drug-resistant mutants, toxicity, and side effects. Inhalable powder formulations of repurposed drugs entail engineering techniques such as micro- or nanoparticulate carriers enabling drug emission by Dry Powder Inhaler devices, deposition onto alveolar epithelia, and transport into AM. Within this context, Solid Lipid Nanoparticle assemblies (SLNas) loaded with rifampicin, a clinically useful anti-TB drug, were produced by processing accepted excipients for DPI formulations through an optimized methodology that avoids organic solvents and is suitable for a large-scale production. The prototypes were functionalized by means of newly synthesized AM receptor-specific targeting agents as the ligands anchored on SLNas surface without chemical reactions. In vitro and in vivo preclinical studies highlighted functionalized SLNas with adequate respirability performance, safety, AM internalization ability, and mice lung deposition in an encouraging perspective of a potential efficacious pulmonary TB therapy. This research was supported by a grant on the project “FAR interdisciplinare 2017” from the University of Modena and Reggio Emilia, Modena, Italy (PI Prof. Luca Costantino)

Novel engineered lipid-based nanoparticles for pulmonary tuberculosis inhalation therapy / Maretti, Eleonora; Truzzi, Eleonora; Costantino, Luca; Rustichelli, Cecilia; Martins Lima, Eliana; Leite Nascimento, Thais; Siligardi, Cristina; Gualtieri, Eva Magdalena; Miselli, Paola; Buttini, Francesca; Leo, Eliana Grazia; Iannuccelli, Valentina. - (2019). ((Intervento presentato al convegno NanoInnovation 2019 tenutosi a Roma nel 11-14 giugno 2019.

Novel engineered lipid-based nanoparticles for pulmonary tuberculosis inhalation therapy

Eleonora Maretti;Eleonora Truzzi;Luca Costantino;Cecilia Rustichelli;Cristina Siligardi;Magdalena Lassinantti Gualtieri;Paola Miselli;Eliana Leo;Valentina Iannuccelli
2019-01-01

Abstract

Priorities to achieve the WHO goal of ending tuberculosis (TB) epidemic by 2030 include new drug treatments to simplify and shorter conventional drug regimens. TB is caused by Mycobacterium tuberculosis residing and surviving inside alveolar macrophages (AM). Considering that 75-80% of cases of infection remain localized in the lungs, the easiest and most successful therapy could involve the inhalation route offering benefits in terms of patient’s autonomy and compliance, by-passing hepatic metabolism, reducing dose amount, dose frequency, and treatment duration, thus minimising the risk of drug-resistant mutants, toxicity, and side effects. Inhalable powder formulations of repurposed drugs entail engineering techniques such as micro- or nanoparticulate carriers enabling drug emission by Dry Powder Inhaler devices, deposition onto alveolar epithelia, and transport into AM. Within this context, Solid Lipid Nanoparticle assemblies (SLNas) loaded with rifampicin, a clinically useful anti-TB drug, were produced by processing accepted excipients for DPI formulations through an optimized methodology that avoids organic solvents and is suitable for a large-scale production. The prototypes were functionalized by means of newly synthesized AM receptor-specific targeting agents as the ligands anchored on SLNas surface without chemical reactions. In vitro and in vivo preclinical studies highlighted functionalized SLNas with adequate respirability performance, safety, AM internalization ability, and mice lung deposition in an encouraging perspective of a potential efficacious pulmonary TB therapy. This research was supported by a grant on the project “FAR interdisciplinare 2017” from the University of Modena and Reggio Emilia, Modena, Italy (PI Prof. Luca Costantino)
NanoInnovation 2019
Roma
11-14 giugno 2019
Maretti, Eleonora; Truzzi, Eleonora; Costantino, Luca; Rustichelli, Cecilia; Martins Lima, Eliana; Leite Nascimento, Thais; Siligardi, Cristina; Gualtieri, Eva Magdalena; Miselli, Paola; Buttini, Francesca; Leo, Eliana Grazia; Iannuccelli, Valentina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1178713
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