Development of polymer nanocomposites for the oral delivery of S-nitrosoglutathione devoted to cardiovascular disease treatment

Abstract : As a physiologic nitric oxide (NO) donor, S-nitrosoglutathione (GSNO) has potential therapeutic application for the treatment of cardiovascular disease (CVD). With a longer in vivo half-life than NO, GSNO is still sensitive to many factors leading to poor applicability. This study aimed at the development of nanocomposite particles (NCP) based on synthetic polymeric nanoparticles encapsulating GSNO (GSNO-NP) embedded in a polysaccharidic matrix for oral delivery of GSNO. Although GSNO-NP, with a high encapsulation efficiency, showed an in vitro burst release, they succeeded in the preservation of GSNO stability and bioavailability for smooth muscle cells as they delayed in vitro protein S-nitrosation (NO biomarker) until 18 h. Therefore, to reach the sustained release, GSNO-NP were embedded in a matrix of alginate (a), chitosan (c) or a blend (acNCP). GSNO-acNCP with high encapsulation efficiency (76%) and an in vitro release until 24 h, promoted the highest permeation rate of GSNO through an intestinal barrier model (Caco-2). With this daily oral treatment compatibility Wistar Rat pretreatment by gavage with GSNO-acNCP 17 h before aorta removal decreased the maximal contractile effect induced by phenylephrine (PHE) on isolated aortic rings. Furthermore, the N-acetylcysteine (a thiol displacing NO stores from tissues) produced the relaxation of PHE precontracted aortic rings, proving NO storage in the vessel wall. By increasing the residence time in the gastrointestinal tract thus promoting GSNO crossing through the intestinal barrier, GSNO-acNCP induced a long lasting effect (17 h after administration) through NO storage in vessels
Document type :
Theses
File URL :
http://docnum.univ-lorraine.fr/prive/DDOC_T_2015_0115_WU.pdf
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01751822
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 1:27:35 PM
Last modification on : Friday, March 30, 2018 - 1:28:55 AM

Identifiers

  • HAL Id : tel-01751822, version 1

Citation

Wen Wu. Development of polymer nanocomposites for the oral delivery of S-nitrosoglutathione devoted to cardiovascular disease treatment. Human health and pathology. Université de Lorraine, 2015. English. ⟨NNT : 2015LORR0115⟩. ⟨tel-01751822⟩

Share

Metrics

Record views

22