title: Time lasting S-nitrosoglutathione polymeric nanoparticles delay cellular protein S-nitrosation.
abstract: Physiological S-nitrosothiols (RSNO), such as S-nitrosoglutathione (GSNO), can be used as nitric oxide (NO) donor for the treatment of vascular diseases. However, despite a half-life measured in hours, the stability of RSNO, limited by enzymatic and non-enzymatic degradations, is too low for clinical application. So, to provide a long-lasting effect and to deliver appropriate NO concentrations to target tissues, RSNO have to be protected. RSNO encapsulation is an interesting response to overcome degradation and provide protection. However, RSNO such as GSNO raise difficulties for encapsulation due to its hydrophilic nature and the instability of the S-NO bound during the formulation process. To our knowledge, the present study is the first description of the direct encapsulation of GSNO within polymeric nanoparticles (NP). The GSNO-loaded NP (GSNO-NP) formulated by a double emulsion process, presented a mean diameter of 289 ± 7 nm. They were positively charged (+40 mV) due to the methacrylic acid and ethylacrylate polymer (Eudragit® RL) used and encapsulated GSNO with a satisfactory efficiency (i.e. 54% or 40 mM GSNO loaded in the NP). In phosphate buffer (37 °C; pH 7.4), GSNO-NP released 100% of encapsulated GSNO within 3h and remained stable still 6h. However, in contact with smooth muscle cells, maximum protein nitrosation (a marker of NO bioavailability) was delayed from 1h for free GSNO to 18h for GSNO-NP. Therefore, protection and sustained release of NO were achieved by the association of a NO donor with a drug delivery system (such as polymeric NP), providing opportunities for vascular diseases treatment.
authors.affiliation: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France. Electronic address: caroline.gaucher@univ-lorraine.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Gaucher
authors.affiliation: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors.forename: Roudayna
authors.initials: R
authors.lastname: Diab
authors.affiliation: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fries
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: Yu-Ling
authors.initials: YL
authors.lastname: Xiao
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: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
authors.affiliation: Université de Lorraine, CITHEFOR EA3452, Faculté de Pharmacie, Nancy, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sapin-Minet
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods; D006207:Half-Life; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D015538:Nitrosation / Q000187:drug effects*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D017293:Protein S / Q000378:metabolism*; D051381:Rats; D026422:S-Nitrosoglutathione / Q000737:chemistry / Q000494:pharmacology*; D026403:S-Nitrosothiols / Q000378:metabolism
chemical_list: D020030:Nitric Oxide Donors; D011108:Polymers; D017293:Protein S; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione
keywords: Drug delivery; Nitric oxide donors; Polymeric nanoparticles; Protein S-nitrosation; S-nitrosoglutathione; Vascular diseases treatment