Imperial College London
Alternate

DrNicholasKirkby

Faculty of Medicine, National Heart & Lung Institute

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3075n.kirkby

 
 
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Location

 

364Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mohamed:2021:10.1038/s41598-021-83423-6,
author = {Mohamed, NA and Abou-Saleh, H and Kameno, Y and Marei, I and de, Nucci G and Ahmetaj-Shala, B and Shala, F and Kirkby, NS and Jennings, L and Al-Ansari, DE and Davies, RP and Lickiss, PD and Mitchell, JA},
doi = {10.1038/s41598-021-83423-6},
journal = {Scientific Reports},
pages = {1--8},
title = {Studies on metal-organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1038/s41598-021-83423-6},
volume = {11},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pulmonary arterial hypertension (PAH) is an incurable disease, although symptoms are treated with a range of dilator drugs. Despite their clinical benefits, these drugs are limited by systemic side-effects. It is, therefore, increasingly recognised that using controlled drug-release nanoformulation, with future modifications for targeted drug delivery, may overcome these limitations. This study presents the first evaluation of a promising nanoformulation (highly porous iron-based metal–organic framework (MOF); nanoMIL-89) as a carrier for the PAH-drug sildenafil, which we have previously shown to be relatively non-toxic in vitro and well-tolerated in vivo. In this study, nanoMIL-89 was prepared and charged with a payload of sildenafil (generating Sil@nanoMIL-89). Sildenafil release was measured by Enzyme-Linked Immunosorbent Assay (ELISA), and its effect on cell viability and dilator function in mouse aorta were assessed. Results showed that Sil@nanoMIL-89 released sildenafil over 6 h, followed by a more sustained release over 72 h. Sil@nanoMIL-89 showed no significant toxicity in human blood outgrowth endothelial cells for concentrations up to100µg/ml; however, it reduced the viability of the human pulmonary artery smooth muscle cells (HPASMCs) at concentrations > 3 µg/ml without inducing cellular cytotoxicity. Finally, Sil@nanoMIL-89 induced vasodilation of mouse aorta after a lag phase of 2–4 h. To our knowledge, this study represents the first demonstration of a novel nanoformulation displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of our nanoformulation, including in PAH models, is required and constitutes the subject of ongoing investigations.
AU  - Mohamed,NA
AU  - Abou-Saleh,H
AU  - Kameno,Y
AU  - Marei,I
AU  - de,Nucci G
AU  - Ahmetaj-Shala,B
AU  - Shala,F
AU  - Kirkby,NS
AU  - Jennings,L
AU  - Al-Ansari,DE
AU  - Davies,RP
AU  - Lickiss,PD
AU  - Mitchell,JA
DO  - 10.1038/s41598-021-83423-6
EP  - 8
PY  - 2021///
SN  - 2045-2322
SP  - 1
TI  - Studies on metal-organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-021-83423-6
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000621916700014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41598-021-83423-6
UR  - http://hdl.handle.net/10044/1/87677
VL  - 11
ER  -
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