Abstract
Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic-co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future.
Highlights
IntroductionHypertension (high blood pressure), as a global public health risk, is highly associated with heart disease, stroke, kidney failure, premature death and disability [1]
Hypertension, as a global public health risk, is highly associated with heart disease, stroke, kidney failure, premature death and disability [1]
VP5 nanoparticles (VP5-NPs) were successfully produced by systematically optimizing the factors that could affect the features of NPs, including the amount of Poly-(lactic-co-glycolic) acid (PLGA), the volume of acetone, pH and the volume of inner aqueous phase, the concentration and volume of poly (PVA), and the sonication time
Summary
Hypertension (high blood pressure), as a global public health risk, is highly associated with heart disease, stroke, kidney failure, premature death and disability [1]. Many anti-hypertensive therapeutic drugs have been developed and are available for clinical treatment, including thiazide diuretics, beta-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors and calcium channel blockers. Side effects have been reported with these treatments. Thiazide diuretics could potentially result in insulin resistance, dyslipidemia, and hyperuricemia, which would accelerate diabetes progression in patients with obesity and/or metabolic syndromes [2]. Traditional β-blockers appear to have a significantly higher risk of diabetes. RAAS inhibition, by an angiotensin converting enzyme (ACE) or an angiotensin receptor blocker (ARB) along with calcium channel blockers, appears to have improved safety properties, but some of them still have various side effects such as coughing, taste disturbances and skin rashes [3]. Future investigations for novel and safe antihypertensive drugs are still required
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