Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway
Nanostructured lipid carriers (NLCs) are an emerging drug delivery platform for improved drug stability and the bioavailability of antihypertensive drugs and vasoprotective nutraceutical compounds, such as resveratrol (RV). The objective of this study was to ascertain NLCs’ potential to deliver RV a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1852 |
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| author | Cai Astley Chahinez Houacine Azziza Zaabalawi Fiona Wilkinson Adam P. Lightfoot Yvonne Alexander Debra Whitehead Kamalinder K. Singh May Azzawi |
| author_facet | Cai Astley Chahinez Houacine Azziza Zaabalawi Fiona Wilkinson Adam P. Lightfoot Yvonne Alexander Debra Whitehead Kamalinder K. Singh May Azzawi |
| author_sort | Cai Astley |
| collection | DOAJ |
| description | Nanostructured lipid carriers (NLCs) are an emerging drug delivery platform for improved drug stability and the bioavailability of antihypertensive drugs and vasoprotective nutraceutical compounds, such as resveratrol (RV). The objective of this study was to ascertain NLCs’ potential to deliver RV and restore attenuated dilator function, using an ex vivo model of acute hypertension. Trimyristin–triolein NLCs were synthesized and loaded with RV. The uptake of RV-NLCs by human coronary artery endothelial cells (HCAECs) maintained their viability and reduced both mitochondrial and cytosolic superoxide levels. Acute pressure elevation in isolated coronary arteries significantly attenuated endothelial-dependent dilator responses, which were reversed following incubation in RV-NLCs, superoxide dismutase or apocynin (<i>p</i> < 0.0001). RV-NLCs demonstrated a five-fold increase in potency in comparison to RV solution. At elevated pressure, in the presence of RV-NLCs, incubation with Nω-nitro-l-arginine (L-NNA) or indomethacin resulted in a significant reduction in the restored dilator component (<i>p</i> < 0.0001), whereas apamin and TRAM-34 had no overall effect. Incubation with the adenosine monophosphate-activated protein kinase (AMPK) inhibitor dorsomorphin significantly attenuated dilator responses (<i>p</i> < 0.001), whereas the SIRT-1 inhibitor EX-527 had no effect. RV-NLCs improved the impaired endothelial-dependent dilation of small coronary arteries, following acute pressure elevation, via NO and downstream COX elements, mediated by AMPK. We suggest that RV-NLCs are an effective delivery modality for improved potency and sustained drug release into the vasculature. Our findings have important implications for the future design and implementation of antihypertensive treatment strategies. |
| first_indexed | 2024-03-10T04:33:21Z |
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| id | doaj.art-048910f2520e4c2c9629b2b79c55b82a |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T04:33:21Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-048910f2520e4c2c9629b2b79c55b82a2023-11-23T03:56:37ZengMDPI AGBiomedicines2227-90592021-12-01912185210.3390/biomedicines9121852Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK PathwayCai Astley0Chahinez Houacine1Azziza Zaabalawi2Fiona Wilkinson3Adam P. Lightfoot4Yvonne Alexander5Debra Whitehead6Kamalinder K. Singh7May Azzawi8Centre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKSchool of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UKCentre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKCentre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKCentre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKCentre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKDepartment of Natural Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKSchool of Pharmacy and Biomedical Sciences, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UKCentre for Bioscience, Department of Life Sciences, Manchester Metropolitan University, Chester Street, Manchester M1 5GD, UKNanostructured lipid carriers (NLCs) are an emerging drug delivery platform for improved drug stability and the bioavailability of antihypertensive drugs and vasoprotective nutraceutical compounds, such as resveratrol (RV). The objective of this study was to ascertain NLCs’ potential to deliver RV and restore attenuated dilator function, using an ex vivo model of acute hypertension. Trimyristin–triolein NLCs were synthesized and loaded with RV. The uptake of RV-NLCs by human coronary artery endothelial cells (HCAECs) maintained their viability and reduced both mitochondrial and cytosolic superoxide levels. Acute pressure elevation in isolated coronary arteries significantly attenuated endothelial-dependent dilator responses, which were reversed following incubation in RV-NLCs, superoxide dismutase or apocynin (<i>p</i> < 0.0001). RV-NLCs demonstrated a five-fold increase in potency in comparison to RV solution. At elevated pressure, in the presence of RV-NLCs, incubation with Nω-nitro-l-arginine (L-NNA) or indomethacin resulted in a significant reduction in the restored dilator component (<i>p</i> < 0.0001), whereas apamin and TRAM-34 had no overall effect. Incubation with the adenosine monophosphate-activated protein kinase (AMPK) inhibitor dorsomorphin significantly attenuated dilator responses (<i>p</i> < 0.001), whereas the SIRT-1 inhibitor EX-527 had no effect. RV-NLCs improved the impaired endothelial-dependent dilation of small coronary arteries, following acute pressure elevation, via NO and downstream COX elements, mediated by AMPK. We suggest that RV-NLCs are an effective delivery modality for improved potency and sustained drug release into the vasculature. Our findings have important implications for the future design and implementation of antihypertensive treatment strategies.https://www.mdpi.com/2227-9059/9/12/1852resveratrolendotheliumcoronary arteryoxidative stressreactive oxygen speciesnanostructured lipid carriers |
| spellingShingle | Cai Astley Chahinez Houacine Azziza Zaabalawi Fiona Wilkinson Adam P. Lightfoot Yvonne Alexander Debra Whitehead Kamalinder K. Singh May Azzawi Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway Biomedicines resveratrol endothelium coronary artery oxidative stress reactive oxygen species nanostructured lipid carriers |
| title | Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway |
| title_full | Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway |
| title_fullStr | Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway |
| title_full_unstemmed | Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway |
| title_short | Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway |
| title_sort | nanostructured lipid carriers deliver resveratrol restoring attenuated dilation in small coronary arteries via the ampk pathway |
| topic | resveratrol endothelium coronary artery oxidative stress reactive oxygen species nanostructured lipid carriers |
| url | https://www.mdpi.com/2227-9059/9/12/1852 |
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