title: Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.
abstract: Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases.
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Perrin-Sarrado
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Hui
authors.initials: H
authors.lastname: Ming
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lartaud
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
authors.affiliation: State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan, China.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Hu
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sapin-Minet
authors.affiliation: CITHEFOR EA3452 "Drug targets, formulation and preclinical assessment", Faculté de Pharmacie, Université de Lorraine, Nancy, France. Electronic address: caroline.gaucher@univ-lorraine.f.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaucher
mesh_terms: D000818:Animals; D001011:Aorta; D018938:Caco-2 Cells; D006801:Humans; D007408:Intestinal Absorption; D053761:Nanocomposites; D009569:Nitric Oxide / Q000378:metabolism*; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000493:pharmacokinetics*
chemical_list: D011108:Polymers; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione
keywords: Isolated aorta vasoreactivity; NO-donor; Oral delivery; Polymer nanocomposites