title: Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles.
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.
authors.affiliation: School of Applied Chemistry and Biological Technology, Shenzhen Polytechnic, Shenzhen 518055, China. tingyu419@126.com.|College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China. tingyu419@126.com.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. tingyu419@126.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China. zhaoshn11@163.com.|State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. zhaoshn11@163.com.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. ziqiangli21@gmail.com.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. Yi_Wang@dfci.harvard.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. xb1990625@126.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. fangdailongtwozero@126.com.
authors.forename: Dailong
authors.initials: D
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. FazhanWang_16@163.com.
authors.forename: Fazhan
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. zhangzhi02@gmail.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China. lilihes@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China. songxr@scu.edu.cn.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.affiliation: School of Applied Chemistry and Biological Technology, Shenzhen Polytechnic, Shenzhen 518055, China. jiany@szpt.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D009842:Oligopeptides; C530287:valyl-leucyl-prolyl-valyl-proline
keywords: PLGA nanoparticles; antihypertensive peptide; continuously antihypertensive effect; oral administration; sustained release