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Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment

Tuberculosis remains one of the world’s deadliest infectious diseases, accounting for nearly 1.3 million deaths every year. Tuberculosis treatment is challenging because of the toxicity, decreased bioavailability at the target site of the conventional drugs and, most importantly, low adherence of pa...

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Autores principales: Hanieh, Patrizia Nadia, Consalvi, Sara, Forte, Jacopo, Cabiddu, Gianluigi, De Logu, Alessandro, Poce, Giovanna, Rinaldi, Federica, Biava, Mariangela, Carafa, Maria, Marianecci, Carlotta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955761/
https://www.ncbi.nlm.nih.gov/pubmed/35335983
http://dx.doi.org/10.3390/pharmaceutics14030610
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author Hanieh, Patrizia Nadia
Consalvi, Sara
Forte, Jacopo
Cabiddu, Gianluigi
De Logu, Alessandro
Poce, Giovanna
Rinaldi, Federica
Biava, Mariangela
Carafa, Maria
Marianecci, Carlotta
author_facet Hanieh, Patrizia Nadia
Consalvi, Sara
Forte, Jacopo
Cabiddu, Gianluigi
De Logu, Alessandro
Poce, Giovanna
Rinaldi, Federica
Biava, Mariangela
Carafa, Maria
Marianecci, Carlotta
author_sort Hanieh, Patrizia Nadia
collection PubMed
description Tuberculosis remains one of the world’s deadliest infectious diseases, accounting for nearly 1.3 million deaths every year. Tuberculosis treatment is challenging because of the toxicity, decreased bioavailability at the target site of the conventional drugs and, most importantly, low adherence of patients; this leads to drug resistance. Here, we describe the development of suitable nanocarriers with specific physicochemical properties to efficiently deliver two potent antimycobacterial compounds. We prepared nanoemulsions and niosomes formulations and loaded them with two different MmpL3 inhibitors previously identified (NEs + BM635 and NIs + BM859). NEs + BM635 and NIs + BM859 were deeply characterized for their physicochemical properties and anti-mycobacterial activity. NEs + BM635 and NIs + BM859 showed good hydrodynamic diameter, ζ-Potential, PDI, drug-entrapment efficiency, polarity, and microviscosity and stability. Even though both formulations proved to perform well, only NIs + BM859 showed potent antimycobacterial activity against M. tuberculosis (MIC = 0.6 µM) compared to that of the free compound. This is most probably caused by the fact that BM635, being highly hydrophobic, encounters maximum hindrance in diffusion, whereas BM859, characterized by high solubility in aqueous medium (152 µM), diffuses more easily. The niosomal formulation described in this work may be a useful therapeutic tool for tuberculosis treatment, and further studies will follow to characterize the in vivo behavior of the formulation.
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spelling pubmed-89557612022-03-26 Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment Hanieh, Patrizia Nadia Consalvi, Sara Forte, Jacopo Cabiddu, Gianluigi De Logu, Alessandro Poce, Giovanna Rinaldi, Federica Biava, Mariangela Carafa, Maria Marianecci, Carlotta Pharmaceutics Article Tuberculosis remains one of the world’s deadliest infectious diseases, accounting for nearly 1.3 million deaths every year. Tuberculosis treatment is challenging because of the toxicity, decreased bioavailability at the target site of the conventional drugs and, most importantly, low adherence of patients; this leads to drug resistance. Here, we describe the development of suitable nanocarriers with specific physicochemical properties to efficiently deliver two potent antimycobacterial compounds. We prepared nanoemulsions and niosomes formulations and loaded them with two different MmpL3 inhibitors previously identified (NEs + BM635 and NIs + BM859). NEs + BM635 and NIs + BM859 were deeply characterized for their physicochemical properties and anti-mycobacterial activity. NEs + BM635 and NIs + BM859 showed good hydrodynamic diameter, ζ-Potential, PDI, drug-entrapment efficiency, polarity, and microviscosity and stability. Even though both formulations proved to perform well, only NIs + BM859 showed potent antimycobacterial activity against M. tuberculosis (MIC = 0.6 µM) compared to that of the free compound. This is most probably caused by the fact that BM635, being highly hydrophobic, encounters maximum hindrance in diffusion, whereas BM859, characterized by high solubility in aqueous medium (152 µM), diffuses more easily. The niosomal formulation described in this work may be a useful therapeutic tool for tuberculosis treatment, and further studies will follow to characterize the in vivo behavior of the formulation. MDPI 2022-03-10 /pmc/articles/PMC8955761/ /pubmed/35335983 http://dx.doi.org/10.3390/pharmaceutics14030610 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hanieh, Patrizia Nadia
Consalvi, Sara
Forte, Jacopo
Cabiddu, Gianluigi
De Logu, Alessandro
Poce, Giovanna
Rinaldi, Federica
Biava, Mariangela
Carafa, Maria
Marianecci, Carlotta
Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title_full Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title_fullStr Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title_full_unstemmed Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title_short Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment
title_sort nano-based drug delivery systems of potent mmpl3 inhibitors for tuberculosis treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955761/
https://www.ncbi.nlm.nih.gov/pubmed/35335983
http://dx.doi.org/10.3390/pharmaceutics14030610
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