A simple and rapid-acting approach for the reduction of C-reactive protein

Momtazi-Borojeni, A. A. and Ayati, S. H. and Jaafari, M. R. and Sahebkar, A. (2019) A simple and rapid-acting approach for the reduction of C-reactive protein. Biomedicine and Pharmacotherapy, 109. pp. 2305-2308.

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Abstract

C-reactive protein (CRP) is an acute-phase protein which can bind to and aggregate oxidized low-density lipoprotein (ox-LDL) particles, thereby enhancing the uptake of oxLDL by macrophages. This finally leads to the formation of foam cells that are a typical characteristic of atherosclerotic plaques. Serum CRP has been shown to bind to phospholipids such as phophatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylserine (PS). Owing to the rapid and efficient clearance of nanoliposomes from the circulation by the liver, we hypothesized that nanoliposomes composed of the mentioned phospholipids can serve as a potential tool to lower elevated serum CRP levels following acute inflammation. To evaluate this hypothesis, nanoliposomal formulations containing hydrogenated soy phosphatidylcholine (HSPC), a combination of HSPC and 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG), and a combination of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) were prepared using lipid film hydration method followed by extrusion at the final concentration of 20 mM. To elevate circulating CRP levels in mice, 0.1 ml of Freund's complete adjuvant (CFA) containing 5 mg/ml heat-killed Mycobacterium tuberculosis was subcutaneously injected into the hind paw of the mice. CFA-challenged mice were intravenously treated with nanoliposomal formulations at the dose of 250 μmol/kg 16 h after CFA challenge that is coincided with peak serum CRP level. After 2 h, the blood was collected and serum level of CRP was measured using a quantitative sandwich enzyme-linked immunosorbent assay. All nanoliposomal formulations showed a size range from 100 to 150 nm in diameter and a polydispersity index of < 0.1. Results showed that all nanoliposomal formulations including DOPC/DOPS, HSPC and HSPC/DSPG could significantly decrease serum levels of CRP by 82.76 (74.44–86.92, p = 0.0001), 44.41 (35.79–50.21, p = 0.0001) and 38.47 (17.21–43.52, p=0.0002) Median (interquartile range), respectively, when compared with the control group. Dexamethasone as a standard could decrease serum CRP level by 27.47% (16.32–31.63%, p = 0.0025) which was a smaller effect compared with the nanoliposomal preparations. In conclusion, negatively charged nanoliposomes could efficiently reduce the elevated serum levels of CRP in CFA-challenged mice. © 2018

Item Type: Article
Additional Information: Export Date: 16 February 2020 CODEN: BIPHE Correspondence Address: Sahebkar, A.; Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, P.O. Box: 91779-48564, Iran; email: sahebkara@mums.ac.ir
Uncontrolled Keywords: Atherosclerosis C-reactive protein Inflammation Liposome Phospholipid C reactive protein dexamethasone dioleoylphosphatidylcholine hydrogenated soy phosphatidylcholine phosphatidylcholine phosphatidylglycerol phosphatidylserine unclassified drug nanoparticle Article atherosclerotic plaque comparative study controlled study coronary artery atherosclerosis dispersity drug formulation enzyme linked immunosorbent assay kinetics liposomal delivery male mouse Mycobacterium tuberculosis nonhuman photon correlation spectroscopy priority journal protein analysis protein blood level quantitative analysis steady state zeta potential animal antagonists and inhibitors blood metabolism time factor Animals Liposomes Mice Nanoparticles Phosphatidylcholines Phosphatidylserines Phospholipids Time Factors
Subjects: WW Ophthalmology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib1 lib1
Date Deposited: 21 Jun 2020 09:19
Last Modified: 21 Jun 2020 09:19
URI: http://eprints.mums.ac.ir/id/eprint/18535

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