Nanoparticle approaches for the renin-angiotensin system

Abstract

The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor penetration across the blood-brain barrier, low bioavailability, and to some extent, short half-lives. Nanoparticle-mediated drug delivery systems (DDSs) are possible emerging alternatives to overcome such limitations. Nanoparticles are ideally 1-100 nm in size and are considered efficient DDSs mainly due to their unique characteristics, including water dispersity, prolonged half-life in blood circulation, smaller size, and biocompatibility. Nano-scale DDSs can reduce the drug dosage frequency and acute toxicity of drugs while enhancing therapeutic success. Different types of nanoparticles, such as chitosan, polymeric, and nanofibers, have been examined in RAS-related studies, especially in hypertension, cardiovascular disease, and COVID-19. In this review article, we summarize the physical and chemical characteristics of each nanoparticle to elaborate on their potential use in RAS-related nano-drug delivery research and clinical application.

Keywords: COVID-19; Cardiovascular disease; Drug delivery; Hypertension; Nanoparticles; Renin-angiotensin system.

Graphical abstract

Fig. 1

The schematic diagram of the classical RAS (ACE/AngII/ATIR axis and the counterregulatory ACE2/Ang1-7/Mas axis arm). The figure represents only the AT1 receptor-rich organs.

Fig. 2

3-dimensional AFM image of the chitosan NPs. The figure was reprinted from Ref. [11] with the permission of the publisher.

Fig. 3

Systolic blood pressure measurements of the SHR for the non-treated control group, free aliskiren, free PLA-NP, and aliskiren-PLA-NP treated group [32]. Reprinted from Ref. [32] with the permission of the publisher.

Fig. 4

The characteristics of the VP5-NPs a) Particle size, b) Potential distribution, c) The appearance under room light and the Tyndall effect, and d) the TEM image [110]. The figure was reprinted from Yu et al., 2016 [110] with the permission of the publisher.

Fig. 5

The SEM images with the corresponding histograms below the image of the (a) free PLA NP and (b) Aliskiren loaded PLA-NP. The figure was reprinted from Ref. [118] with permission of the publisher.

Fig. 6

Confocal imaging of AT1R (red) and TDCNfs (green) inOGD rat cardiac myocytes. NBDAng1-7, NBDSAA1-7 showed no binding to the OGD myocytes, while TDCNfs colocalized with the OGD myocytes (yellow). The three single channel images are shown as smaller images to the right of the colocalization images. Scale bar 25 μM. The figure was reprinted from Ref. [31] upon the permission of the publisher.

Fig. 7

A) First two steps represents the shematic diagram of the synthesis of the monoclonal anti-tau aggregate antibody conjugated gold nanoparticles wherease the last step represents the color change of the anti-tau aggregate antibody conjugated gold nanoparticles when they bind to the tau protein aggregate. B) TEM image of the anti-tau antibody conjugated gold nanoparticles C) TEM image of the anti-tau antibody conjugated gold nanoparticle after the binding with tau protein. Figure was reprinted from Ref. [136] under the persmison of the publisher.