Metal Organic Framework as a Potential Drug Carrier for Pulmonary Arterial Hypertension

2016 ◽  
Author(s):  
Nura Adam Mohamed ◽  
Rob Davies ◽  
Paul D. Lickiss ◽  
Hira Saleem ◽  
Daniel M. Reed ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Metal Organic Framework ◽  
Drug Carrier ◽  
Potential Drug ◽  
Metal Organic ◽  
Pulmonary Arterial ◽  
Organic Framework

scholarly journals Metal-organic framework (MOF) nanomedicine preparations of sildenafil designed for the future treatment of pulmonary arterial hypertension

2019 ◽  
Author(s):  
Nura A. Mohamed ◽  
Haissam Abou Saleh ◽  
Yu Kameno ◽  
Isra Marei ◽  
Gilberto de Nucci ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Drug Release ◽  
Arterial Hypertension ◽  
Metal Organic Framework ◽  
Porous Iron ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Metal Organic ◽  
Pulmonary Arterial ◽  
Nano Formulation ◽  
Organic Framework

AbstractPulmonary Arterial Hypertension (PAH) is an aggressive disease with poor prognosis, no available cure, and low survival rates. Currently, there are several classes of vasodilator drugs that are widely used as treatment strategies for PAH. These include (i) endothelin-1 receptor antagonists, (ii) phosphodiesterase type 5 inhibitors, (iii) prostacyclin analogues, and (iv) soluble guanylate cyclase activators. Despite their clinical benefits, these therapies are hindered by their systemic side effects. This limitation could be overcome by controlled drug release, with future modifications for targeted drug delivery, using a nanomedicine approach. In the current study, we have evaluated one particular nanomedicine platform (the highly porous iron-based metal-organic framework (MOF) commonly referred to as MIL-89) as a carrier of the PAH drug sildenafil. We have previously shown that MIL-89 is relatively non-toxic in a range of human cell types and well tolerated in vivo. Here we prepared a nano-formulation of MIL-89 (nanoMIL-89) and then successfully charged it with a payload of sildenafil (sil@nanoMIL-891). sil@nanoMIL-89 was then shown to release sildenafil in a biphasic manner with an initial rapid release over 6 hours followed by a more sustained release over 72 hours. Both nanoMIL-89 and sil@nanoMIL-89 were relatively non-toxic when incubated with human endothelial cells for 24 hours. Finally, the vasodilator effect of sil@nanoMIL-89 was measured over 8 hours using isolated mouse aorta. Consistent with drug release kinetics, sil@nanoMIL-89 induced vasodilation after a lag phase of >4 hours. Thus, in sil@nanoMIL-89, we have produced a nano-formulation of sildenafil displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of sil@nanoMIL-89, including in PAH models, is now required and constitutes the subject of ongoing investigation.

scholarly journals Studies on metal–organic framework (MOF) nanomedicine preparations of sildenafil for the future treatment of pulmonary arterial hypertension

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nura A. Mohamed ◽  
Haissam Abou-Saleh ◽  
Yu Kameno ◽  
Isra Marei ◽  
Gilberto de Nucci ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Drug Release ◽  
Arterial Hypertension ◽  
Metal Organic Framework ◽  
Enzyme Linked Immunosorbent Assay ◽  
Porous Iron ◽  
Metal Organic ◽  
Pulmonary Arterial ◽  
Mouse Aorta ◽  
Organic Framework

AbstractPulmonary 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.

Improving the genistein oral bioavailability via its formulation into the metal–organic framework MIL-100(Fe)

2021 ◽  
Vol 9 (9) ◽  
pp. 2233-2239
Author(s):  
Adrià Botet-Carreras ◽  
Cristina Tamames-Tabar ◽  
Fabrice Salles ◽  
Sara Rojas ◽  
Edurne Imbuluzqueta ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Metal Organic Framework ◽  
Drug Carrier ◽  
Aqueous Solubility ◽  
Carrier System ◽  
System P ◽  
Metal Organic ◽  
Drug Carrier System ◽  
Organic Framework

Despite the interesting chemopreventive, antioxidant and antiangiogenic effects of the natural bioflavonoid genistein (GEN), its low aqueous solubility and bioavailability make it necessary to administer it using a suitable drug carrier system.

Mesoporous metal–organic framework MIL-100(Fe) as drug carrier

Adsorption ◽  
2021 ◽  
Author(s):  
Paulo G. M. Mileo ◽  
Diony N. Gomes ◽  
Daniel V. Gonçalves ◽  
Sebastião M. P. Lucena
Keyword(s):  
Metal Organic Framework ◽  
Drug Carrier ◽  
Metal Organic ◽  
Mesoporous Metal ◽  
Organic Framework

One-pot synthesis of a metal–organic framework-based drug carrier for intelligent glucose-responsive insulin delivery

2018 ◽  
Vol 54 (42) ◽  
pp. 5377-5380 ◽  
Author(s):  
Yan Duan ◽  
Fanggui Ye ◽  
Yuanlin Huang ◽  
Yuemei Qin ◽  
Caimei He ◽  
...  
Keyword(s):  
Metal Organic Framework ◽  
Drug Carrier ◽  
Insulin Delivery ◽  
Glucose Stimulation ◽  
One Pot ◽  
One Pot Synthesis ◽  
Metal Organic ◽  
Organic Framework

A glucose-responsive metal–organic framework (MOF)-based insulin delivery nanosystem was developed via a one-pot process. The system relies on the MOF response to glucose stimulation and this can promote insulin delivery.

scholarly journals In Vitro Toxicity Study of a Porous Iron(III) Metal‒Organic Framework

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1211 ◽  
Author(s):  
Gongsen Chen ◽  
Xin Leng ◽  
Juyuan Luo ◽  
Longtai You ◽  
Changhai Qu ◽  
...  
Keyword(s):  
Metal Organic Framework ◽  
Drug Carrier ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Porous Iron ◽  
Dapi Staining ◽  
Toxicological Assessment ◽  
Metal Organic ◽  
Organic Framework

A MIL series metal‒organic framework (MOF), MIL-100(Fe), was successfully synthesized at the nanoscale and fully characterized by TEM, TGA, XRD, FTIR, DLS, and BET. A toxicological assessment was performed using two different cell lines: human normal liver cells (HL-7702) and hepatocellular carcinoma (HepG2). In vitro cytotoxicity of MIL-100(Fe) was evaluated by the MTT assay, LDH releasing rate assay, DAPI staining, and annexin V/PI double staining assay. The safe dose of MIL-100(Fe) was 80 μg/mL. It exhibited good biocompatibility, low cytotoxicity, and high cell survival rate (HL-7702 cells’ viability >85.97%, HepG2 cells’ viability >91.20%). Therefore, MIL-100(Fe) has a potential application as a drug carrier.

scholarly journals Internalization of Metal–Organic Framework Nanoparticles in Human Vascular Cells: Implications for Cardiovascular Disease Therapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1028
Author(s):  
Dana E. Al-Ansari ◽  
Nura A. Mohamed ◽  
Isra Marei ◽  
Atef Zekri ◽  
Yu Kameno ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Imaging Techniques ◽  
Metal Organic Framework ◽  
Microscopy Imaging ◽  
Cellular Assays ◽  
Future Drug ◽  
Metal Organic ◽  
Pulmonary Arterial ◽  
Endocytic Vesicles ◽  
Organic Framework

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Alteration of endothelial cells and the underlying vasculature plays a central role in the pathogenesis of various CVDs. The application of nanoscale materials such as nanoparticles in biomedicine has opened new horizons in the treatment of CVDs. We have previously shown that the iron metal–organic framework nanoparticle, Materials Institut Lavoisier-89 (nanoMIL-89) represents a viable vehicle for future drug delivery of pulmonary arterial hypertension. In this study, we have assessed the cellular uptake of nanoMIL-89 in pulmonary artery endothelial and smooth muscle cells using microscopy imaging techniques. We also tested the cellular responses to nanoMIL-89 using molecular and cellular assays. Microscopic images showed cellular internalization of nanoMIL-89, packaging into endocytic vesicles, and passing to daughter cells during mitosis. Moreover, nanoMIL-89 showed anti-inflammatory activity without any significant cytotoxicity. Our results indicate that nanoMIL-89 formulation may offer promising therapeutic opportunities and set forth a new prototype for drug delivery not only in CVDs, but also for other diseases yet incurable, such as diabetes and cancer.

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