title: Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery.
abstract: S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor with therapeutic potential for cardiovascular disease treatment. Chronic oral treatment with GSNO is limited by high drug sensitivity to the environment and limited oral bioavailability, requiring the development of delivery systems able to sustain NO release. The present work describes new platforms based on polymer nanocomposite particles for the delivery of GSNO. Five types of optimized nanocomposite particles have been developed (three based on chitosan, two based on alginate sodium). Those nanocomposite particles encapsulate GSNO with high efficiency from 64% to 70% and an average size of 13 to 61 μm compatible with oral delivery. Sustained release of GSNO in vitro was achieved. Indeed, chitosan nanocomposites discharged their payload within 24h; whereas alginate nanocomposites released GSNO more slowly (10% of GSNO was still remaining in the dosage form after 24h). Their cytocompatibility toward intestinal Caco-2 cells (MTT assay) was acceptable (IC50: 6.07 ± 0.07-9.46 ± 0.08 mg/mL), demonstrating their suitability as oral delivery systems for GSNO. These delivery systems presented efficient GSNO loading and sustained release as well as cytocompatibility, showing their promise as a means of improving the oral bioavailability of GSNO and as a potential new treatment.
authors: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors: Wen
authors: W
authors: Wu
authors: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France. Electronic address: caroline.gaucher@univ-lorraine.fr.
authors: Caroline
authors: C
authors: Gaucher
authors: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors: Isabelle
authors: I
authors: Fries
authors: 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: Xian-Ming
authors: XM
authors: Hu
authors: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors: Philippe
authors: P
authors: Maincent
authors: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors: Anne
authors: A
authors: Sapin-Minet
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D053761:Nanocomposites / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D010316:Particle Size; D026422:S-Nitrosoglutathione / Q000008:administration & dosage*
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D020030:Nitric Oxide Donors; D026422:S-Nitrosoglutathione; D020723:Glucuronic Acid; D048271:Chitosan
keywords: Alginate; Chitosan; Oral delivery; Polymer nanocomposite particles; S-nitrosoglutathione; Sustained release