Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta

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• 作者：Wen Wu ; PharmD ; PhD^a ; Caroline Perrin-Sarrado ; PharmD ; PhD^a ; Hui Ming ; PharmD^a ; Isabelle Lartaud ; PharmD ; PhD^a ; Philippe Maincent ; PharmD ; PhD^a ; Xian-Ming Hu ; PhD^b ; Anne Sapin-Minet ; PhD^a ; Caroline Gaucher ; PhD^a ; ^{caroline.gaucher@univ-lorraine.f" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NO-donor ; Polymer nanocomposites ; Oral delivery ; Isolated aorta vasoreactivity
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：7
• 页码：1795-1803
• 全文大小：571 K

文摘

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.