Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis

• Main Authors: Ahmad Z. Bahlool (Author), Sarinj Fattah (Author), Andrew O'Sullivan (Author), Brenton Cavanagh (Author), Ronan MacLoughlin (Author), Joseph Keane (Author), Mary P. O'Sullivan (Author), Sally-Ann Cryan (Author)
• Format: Book
• Published: MDPI AG, 2022-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than <i>Mtb</i> directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT^® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 μm as measured by cascade impaction, and a volumetric median diameter of 4.09 μm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

Item Description

10.3390/pharmaceutics14081745
1999-4923