title: Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?
abstract: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1 day and 1 week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential.
authors: Université de Lorraine, Faculty of Pharmacy, Nancy Cedex, France.
authors: Marianne
authors: M
authors: Parent
authors: Ariane
authors: A
authors: Boudier
authors: François
authors: F
authors: Dupuis
authors: Cécile
authors: C
authors: Nouvel
authors: Anne
authors: A
authors: Sapin
authors: Isabelle
authors: I
authors: Lartaud
authors: Jean-Luc
authors: JL
authors: Six
authors: Pierre
authors: P
authors: Leroy
authors: Philippe
authors: P
authors: Maincent
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004343:Drug Implants; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011760:Pyrrolidinones / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000008:administration & dosage* / Q000737:chemistry; D026422:S-Nitrosoglutathione / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013686:Telemetry; D014215:Triacetin / Q000737:chemistry; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011760:Pyrrolidinones; D014665:Vasodilator Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; C038678:N-methylpyrrolidone; D014215:Triacetin
keywords: Drug delivery systems; In situ implants; In situ microparticles; Nitric oxide donors; Pulse arterial pressure; S-nitrosothiols; Sustained release