mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs

Imanparast, Fatemeh; Faramarzi, Mohammad Ali; Vatannejad, Akram; Paknejad, Maliheh; Deiham, Behnas; Kobarfard, Farzad; Amani, Amir; Doosti, Mahmood

doi:10.1016/j.mvr.2017.02.002

Cited by 17 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formulation of SV‐NPs improves the pharmacokinetic profile and bioavailability of SV; it was also reported that nanostructured lipid carriers, especially those associated with SV, were able to reduce cytotoxicity. A study based on the HUVEC model also showed that SV‐NPs and the associated targeted drugs could ameliorate endothelial dysfunction . Similarly, our study shows that the barrier protection of SV/SV‐NPs was significant.…”

Section: Discussionsupporting

confidence: 74%

“…A study based on the HUVEC model also showed that SV-NPs and the associated targeted drugs could ameliorate endothelial dysfunction. 28 Similarly, our study shows that the barrier protection of SV/SV-NPs was significant. High-permeability induced by LPS was successfully reversed by SV preparations, and the effect of SV-NPs was better than that of SV.…”

Section: Discussionsupporting

confidence: 70%

“…The clinical application of statins to sepsis patients is presently controversial. Simvastatin nanoparticles (SV‐NPs), a tool for the targeted delivery of SV using nanostructured lipid carriers, are an improved formulation that facilitate the drug's protective effects on endothelial or other cells without increasing the dose and avoiding unnecessary liver and kidney damage . This study therefore investigated whether different SV preparations had protective effects on the vascular endothelium and whether SV preparations repaired LPS‐injured endothelial cells through the IQGAP1/PDGFRβ‐binding complex and related signalling pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Simvastatin nanoparticles (SV-NPs), a tool for the targeted delivery of SV using nanostructured lipid carriers, are an improved formulation that facilitate the drug's protective effects on endothelial or other cells without increasing the dose and avoiding unnecessary liver and kidney damage. [28][29][30] This study therefore investigated whether different SV preparations had protective effects on the vascular endothelium and whether SV preparations repaired LPSinjured endothelial cells through the IQGAP1/PDGFRβ-binding complex and related signalling pathways. were interfered for 24 hours with LPS doses of 10 μg/mL, and SV/ SV-NPs were used at the concentration of 1 μmol/L, LY294002 was used at the concentration of 25 μmol/L, and Imatinib was used at the concentration of 20 μmol/L.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

Zheng

Zhang

Wang

2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Endothelial barrier dysfunction is a critical pathophysiological process of sepsis. Impaired endothelial cell migration is one of the main reasons for endothelial dysfunction. Statins may have a protective effect on endothelial barrier function. However, the effect and mechanism of statins on lipopolysaccharide (LPS)‐induced endothelial barrier dysfunction remain unclear. Simvastatin (SV) was loaded in nanostructured lipid carriers to produce SV nanoparticles (SV‐NPs). Normal SV and SV‐NPs were used to treat human umbilical vein vascular endothelial cells (HUVECs) injured by LPS. Barrier function was evaluated by monitoring cell monolayer permeability and transendothelial electrical resistance, and cell migration ability was measured by a wound healing assay. LY294002 and imatinib were used to inhibit the activity of PI3K/Akt and platelet‐derived growth factor receptor (PDGFR) β. IQ‐GTPase‐activating protein 1 (IQGAP1) siRNA was used to knockdown endogenous IQGAP1, which was used to verify the role of the PDGFRβ/PI3K/Akt/IQGAP1 pathway in SV/SV‐NPs‐mediated barrier protection in HUVECs injured by LPS. The results show that SV/SV‐NPs promoted the migration and decreased the permeability of HUVECs treated with LPS, and the efficacy of the SV‐NPs exceeded that of SV significantly. LY294002, imatinib and IQGAP1 siRNA all suppressed the barrier protection of SV/SV‐NPs. SV/SV‐NPs promoted the secretion of platelet‐derived growth factor‐BB (PDGF‐BB) and activated the PDGFRβ/PI3K/Akt/IQGAP1 pathway. SV preparations restored endothelial barrier function by restoring endothelial cell migration, which is involved in the regulation of the PDGFRβ/PI3K/Akt/IQGAP1 pathway and PDGF‐BB secretion. As an appropriate formulation for restoring endothelial dysfunction, SV‐NPs may be more effective than SV.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

Zheng

Zhang

Wang

2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Moreover, a different study evaluated endothelial dysfunction recovery, aiming to improve atherosclerosis treatment. PLGA nanoparticles loaded with simvastatin were conjugated with a synthetic peptide mZD7349 and investigated in vitro against vascular cell adhesion molecule 1 (VCAM-1) expressed by activated human umbilical cord vascular endothelial cells (HUVECs) ( Imanparast et al, 2017 ). Quantification of endothelial nitric oxide synthase, an enzyme responsible for repairing the vascular endothelium, showed that PLGA nanoparticles loaded with simvastin and conjugated to mZD7349 peptide expressed more of this enzyme compared to those non-conjugated nanoparticles with simvastatin ( Imanparast et al, 2017 ).…”

Section: Nanotechnology Involvement In the Delivery Of Antimicrobial mentioning

confidence: 99%

Antimicrobial Peptides and Nanotechnology, Recent Advances and Challenges

et al. 2018

View full text Add to dashboard Cite

Antimicrobial peptides are sequences of amino acids, which present activity against microorganisms. These peptides were discovered over 70 years ago, and are abundant in nature from soil bacteria, insects, amphibians to mammals and plants. They vary in amino acids number, the distance between amino acids within individual peptide structure, net charge, solubility and other physical chemical properties as well as differ in mechanism of action. These peptides may provide an alternative treatment to conventional antibiotics, which encounter resistance such as the peptide nisin applied in treating methicillin resistant Staphylococcus aureus (MRSA) or may behave synergistically with known antibiotics against parasites for instance, nisin Z when used in synergy with ampicillin reported better activity against Pseudomonas fluorescens than when the antibiotic was alone. AMPs are known to be active against viruses, bacteria, fungi and protozoans. Nanotechnology is an arena which explores the synthesis, characterization and application of an array of delivery systems at a one billionth of meter scale. Such systems are implemented to deliver drugs, proteins, vaccines, and peptides. The role of nanotechnology in delivering AMPs is still at its early development stage. There are challenges of incorporating AMPs into drug delivery system. This review intends to explore in depth, the role of nanotechnology in delivering AMPs as well as presenting the current advances and accompanying challenges of the technology.

show abstract