Studies on metal–organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension
Author | Mohamed, Nura A. |
Author | Abou-Saleh, Haissam |
Author | Kameno, Yu |
Author | Marei, Isra |
Author | de Nucci, Gilberto |
Author | Ahmetaj-Shala, Blerina |
Author | Shala, Fisnik |
Author | Kirkby, Nicholas S. |
Author | Jennings, Lewis |
Author | Al-Ansari, Dana E. |
Author | Davies, Robert P. |
Author | Lickiss, Paul D. |
Author | Mitchell, Jane A. |
Available date | 2023-11-01T07:06:00Z |
Publication Date | 2021-12-01 |
Publication Name | Scientific Reports |
Identifier | http://dx.doi.org/10.1038/s41598-021-83423-6 |
Citation | Mohamed, N.A., Abou-Saleh, H., Kameno, Y. et al. Studies on metal–organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension. Sci Rep 11, 4336 (2021). https://doi.org/10.1038/s41598-021-83423-6 |
Abstract | 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. |
Sponsor | Open Access funding enabled and organized by Projekt DEAL. |
Language | en |
Publisher | nature |
Subject | Drug delivery Nanomedicine Nanoscience and technology |
Type | Article |
Issue Number | 1 |
Volume Number | 11 |
ESSN | 2045-2322 |
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