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المؤلفMohamed, Nura A.
المؤلفAbou-Saleh, Haissam
المؤلفKameno, Yu
المؤلفMarei, Isra
المؤلفde Nucci, Gilberto
المؤلفAhmetaj-Shala, Blerina
المؤلفShala, Fisnik
المؤلفKirkby, Nicholas S.
المؤلفJennings, Lewis
المؤلفAl-Ansari, Dana E.
المؤلفDavies, Robert P.
المؤلفLickiss, Paul D.
المؤلفMitchell, Jane A.
تاريخ الإتاحة2023-11-01T07:06:00Z
تاريخ النشر2021-12-01
اسم المنشورScientific Reports
المعرّفhttp://dx.doi.org/10.1038/s41598-021-83423-6
الاقتباسMohamed, 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
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85101424130&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/48947
الملخصPulmonary 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.
راعي المشروعOpen Access funding enabled and organized by Projekt DEAL.
اللغةen
الناشرnature
الموضوعDrug delivery
Nanomedicine
Nanoscience and technology
العنوانStudies on metal–organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension
النوعArticle
رقم العدد1
رقم المجلد11
ESSN2045-2322
dc.accessType Open Access


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