Imperial College London
Alternate

DrBrianRobertson

Faculty of Medicine, Department of Infectious Disease

Reader in Systems Microbiology
 
 
 
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Contact

 

b.robertson

 
 
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Location

 

3.41Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{O'Connor:2019:10.1016/j.ejpb.2018.10.020,
author = {O'Connor, G and Krishnan, N and Fagan-Murphy, A and Cassidy, J and O'Leary, S and Robertson, BD and Keane, J and O'Sullivan, MP and Cryan, S-A},
doi = {10.1016/j.ejpb.2018.10.020},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
pages = {153--165},
title = {Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-Retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection},
url = {http://dx.doi.org/10.1016/j.ejpb.2018.10.020},
volume = {134},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Ending the tuberculosis (TB) epidemic by 2030 was recently listed in the United Nations (UN) Sustainable Development Goals alongside HIV/AIDS and malaria as it continues to be a major cause of death worldwide. With a significant proportion of TB cases caused by resistant strains of Mycobacterium tuberculosis (Mtb), there is an urgent need to develop new and innovative approaches to treatment. Since 1989, researchers have been assessing the anti-bacterial effects of the active metabolite of vitamin A, all trans-Retinoic acid (ATRA) solution, in Mtb models. More recently the antibacterial effect of ATRA has been shown to regulate the immune response to infection via critical gene expression, monocyte activation and the induction of autophagy leading to its application as a host-directed therapy (HDT). Inhalation is an attractive route for targeted treatment of TB, and therefore we have developed ATRA-loaded microparticles (ATRA-MP) within the inhalable size range (2.07±0.5µm) offering targeted delivery of the encapsulated cargo (70.5±2.3%) to the site of action within the alveolar macrophage, which was confirmed by confocal microscopy. Efficient cellular delivery of ATRA was followed by a reduction in Mtb growth (H37Ra) in THP-1 derived macrophages evaluated by both the BACT/ALERT® system and enumeration of colony forming units (CFU). The antibacterial effect of ATRA-MP treatment was further assessed in BALB/c mice infected with the virulent strain of Mtb (H37Rv). ATRA-MP treatments significantly decreased the bacterial burden in the lungs alongside a reduction in pulmonary pathology following just three doses administered intratracheally. The immunomodulatory effects of targeted ATRA treatment in the lungs indicate a distinct yet effective mechanism of action amongst the formulations. This is the first study to-date of a controlled release ATRA treatment for TB suitable for inhalation that offers improved targeting of a HDT, retains antib
AU  - O'Connor,G
AU  - Krishnan,N
AU  - Fagan-Murphy,A
AU  - Cassidy,J
AU  - O'Leary,S
AU  - Robertson,BD
AU  - Keane,J
AU  - O'Sullivan,MP
AU  - Cryan,S-A
DO  - 10.1016/j.ejpb.2018.10.020
EP  - 165
PY  - 2019///
SN  - 0939-6411
SP  - 153
TI  - Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-Retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis infection
T2  - European Journal of Pharmaceutics and Biopharmaceutics
UR  - http://dx.doi.org/10.1016/j.ejpb.2018.10.020
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000456225000016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/66808
VL  - 134
ER  -
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