Core-shell lipid-polymeric nanoparticles for enhanced oral bioavailability and antihypertensive efficacy of KY5 peptide  

作　　者：Jingmei Yuan Mengran Guo Shengnan Zhao Jinhua Li Xinchun Wang Jian Yang Zhaohui Jin Xiangrong Song 

机构地区：[1]Department of Critical Care Medicine,Department of Clinical Pharmacy,Frontiers Science Center for Disease-related Molecular Network,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610041,China [2]School of Applied Chemistry and Biological Technology,Shenzhen Polytechnic,Shenzhen 518055,China [3]First Affiliated Hospital of the Medical College,Shihezi University,Shihezi 832008,China

出　　处：《Chinese Chemical Letters》2023年第4期158-163,共6页中国化学快报（英文版）

基　　金：supported by the Youth Fund of National Natural Science Foundation of China (No. 82104081);the Science and Technology Project of Shenzhen (No. JCYJ20170413155047512);the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University (No. ZYGD18020/ZYJC18006);the Sichuan Province Science and Technology Support Program (No. 2020JDRC0052);the Science and Technology Project of Xinjiang Production and Construction Corps (No. 2022AB020)。

摘　　要：Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides.

关 键 词：HYPERTENSION Core-shell lipid-polymeric nanoparticles KY5 Antihypertensive peptides Oral delivery 

分 类 号：TQ317[化学工程—高聚物工业] TB383.1[一般工业技术—材料科学与工程] R943[医药卫生—药剂学]