Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?
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- 作者：Marianne Parent ; Ariane Boudier ; Fran莽ois Dupuis ; C茅cile Nouvel ; Anne Sapin ; Isabelle Lartaud ; Jean-Luc Six ; Pierre Leroy ; Philippe Maincent
- 关键词：In situ implants ; In situ microparticles ; S-nitrosothiols ; Nitric oxide donors ; Drug delivery systems ; Sustained release ; Pulse arterial pressure
- 刊名：European Journal of Pharmaceutics and Biopharmaceutics
- 出版年：November, 2013
- 年：2013
- 卷：85
- 期：3_part_PA
- 页码：640-649
- 全文大小：1765 K
文摘
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.