Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 24;13(1):13880.
doi: 10.1038/s41598-023-41136-y.

Anti-inflammation-based treatment of atherosclerosis using Gliclazide-loaded biomimetic nanoghosts

Zahra Karami  1 , Jalil Mehrzad  2 , Mohammad Akrami  3 , Saman Hosseinkhani  4
Affiliations

Anti-inflammation-based treatment of atherosclerosis using Gliclazide-loaded biomimetic nanoghosts

Zahra Karami et al. Sci Rep. .

Abstract

In the study, a biomimetic platform for anti-inflammatory-based treatment of atherosclerotic plaque was developed. Gliclazide (GL) as an anti-inflammasome agent was encapsulated in PLGA nanoparticles (NP), which were coated by monocyte membrane using an extrusion procedure. The size and zeta potential of the nanoghost (NG) changed to 292 and - 10 nm from 189.5 to -34.1 in the core NP. In addition, the actual size of 62.5 nm with a coating layer of 5 nm was measured using TEM. The NG was also showed a sustained release profile with the drug loading content of about 4.7%. Beside to attenuated TNFα, decrease in gene expression levels of NLRP3, MyD88, NOS, IL-1β, IL-18 and caspases 1/3/8/9 in LPS-primed monocytes exposed to NG strongly indicated remarkable inflammation control. After systemic toxicity evaluation and pharmacokinetic analysis of NP and NG, intravenous NG treatment of rabbits with experimentally induced atherosclerosis revealed remarkably less plaque lesions, foam cells, lipid-laden macrophages, and pathological issues in tunica media of aorta sections. Higher expression of CD163 than CD68 in aorta of NG-treated rabbits strongly reveals higher M2/M1 macrophage polarization. The bio/hemocompatible, biomimetic and anti-inflammatory NG can be considered as a potential platform for immunotherapy of particularly atherosclerosis in the field of personalized medicine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
A macrophage-guided biomimetic platform designed here against atherosclerosis. A macrophage-guided biomimetic platform with anti-inflammatory agent, Gliclazide (GL), encapsulated in PLGA nanoparticles and overall coated with monocyte membrane with extrusion technique to generate pharmaceutically applicable nanoghosts for warding off atherosclerosis.
Figure 2
Figure 2
Hydrodynamic size of PLGA nanoparticles (A) and nanoghosts (B) using DLS measurement; TEM (C) and SEM (D) micrograph of drug loaded NG.
Figure 3
Figure 3
(A) Gliclazide release profile from nanoghosts (NG); (B) Hemolytic activity of drug loaded monocytes-based nanoghosts. Error bars show the standard deviation of triplicate measurements, and (C) demonstrates the hemolytic percentages of RBC exposed to different concentrations of NG compared to positive and negative controls.
Figure 4
Figure 4
(A) TNFα assay of GL-loaded NG/NP on LPS-induced monocytes. Results were expressed by concentration (pg/mL) as compared with control. Data represent mean ± SD (n = 3); (B) Expression levels of Caspase1, Caspase3, Caspase8, Caspase9, NLRP3, NOS, MYD88, IL-1beta and IL-18 for LPS primed monocytes exposed to nanoghosts (NG) and nanoparticles (NP) compared to LPS-primed monocytes. Data represent mean ± SD (n = 3). *P-value < 0.05.
Figure 5
Figure 5
(A) The evaluation of systemic toxicity of nanoghost (NP) and nanoparticle (NG) (100 μL of NP and NG containing 6 μg of GL) for NG/NP treated rabbits, compared to control groups upon weigh tracking for a month (n = 8 for each group, P-value < 0.05). (B) The in vivo GL profile of drug-loaded NG and PLGA NPs in the pharmacokinetic study. 100 μL of NP and NG containing 2.88 μg of GL was injected intravenously. Data represent mean ± SD (n = 3).
Figure 6
Figure 6
Semi-quantitative estimation of CD14 + cell percentage (A); CD163:CD68 ratio (B) through histo/immunohistochemistry analysis; Estimation of surface area (µm2) in intimal area of plaques using the Optika software (× 64, 4.11.18081.20201205 (C). Estimation of foam cell percentage (D) for NG/NP treated groups, compared to the normal and the positive group (P-values for all groups versus related positive controls were labeled with * and ** which indicate less than 0.05 and 0.01, respectively; α = 0.05). Data represent mean ± SD (n = 3). Representative hematoxylin–eosin and immuno-histochemical staining (E) for the aorta sections in the rabbit group fed with cholesterol-free feed/negative control (a); NP treated group (b); NG treated group (c) and positive group (d). Black arrows in Eb, Ec and Ed show the location of foam cells. 100 μL of NG and NP containing about 48 ng/mL of Gliclazide was injected into each group (n = 8) daily and every 2 days for 4 weeks, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lusis AJ. Atherosclerosis. Nature. 2000;407:233–241. doi: 10.1038/35025203. - DOI - PMC - PubMed
    1. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145:341–355. doi: 10.1016/j.cell.2011.04.005. - DOI - PMC - PubMed
    1. Otsuka F, et al. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study. Atherosclerosis. 2015;241:772–782. doi: 10.1016/j.atherosclerosis.2015.05.011. - DOI - PMC - PubMed
    1. Feng B, et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat. Cell Biol. 2003;5:781–792. doi: 10.1038/ncb1035. - DOI - PubMed
    1. Kim M, et al. Targeted delivery of anti-inflammatory cytokine by nanocarrier reduces atherosclerosis in Apo E(-/-) mice. Biomaterials. 2020;226:119550. doi: 10.1016/j.biomaterials.2019.119550. - DOI - PubMed

Publication types