Polymer Nanocomposites Enhance S-Nitrosoglutathione Intestinal Absorption And Promote The Formation Of Releasable Nitric Oxide Stores In Rat Aorta

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 17 h, 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. (C) 2016 Published by Elsevier Inc.