Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?

被引：12
作者：
Parent, Marianne [1 ]
Boudier, Ariane [1 ]
Dupuis, Francois [1 ]
Nouvel, Cecile [2 ,3 ]
Sapin, Anne [1 ]
Lartaud, Isabelle [1 ]
Six, Jean-Luc [2 ,3 ]
Leroy, Pierre [1 ]
Maincent, Philippe [1 ]
机构：
[1] Univ Lorraine, Fac Pharm, F-54000 Nancy, France
[2] Univ Lorraine, Lab Chim Phys Macromol, F-54000 Nancy, France
[3] CNRS, Lab Chim Phys Macromol, Nancy, France
来源：
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2013年 / 85卷 / 03期
关键词：
In situ implants; In situ microparticles; S-nitrosothiols; Nitric oxide donors; Drug delivery systems; Sustained release; Pulse arterial pressure; NITRIC-OXIDE RELEASE; PHASE INVERSION DYNAMICS; DRUG-DELIVERY; DONOR DRUGS; IMPLANTS; TOLERANCE; PROTEIN;
D O I：
10.1016/j.ejpb.2013.08.005
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码：640 / 649
页数：10
相关论文
共 36 条
[1]   Injectable implants for the sustained release of protein and peptide drugs [J].
Agarwal, Priyanka ;
Rupenthal, Ilva D. .
DRUG DISCOVERY TODAY, 2013, 18 (7-8) :337-349
[2]   S-nitrosothiols:: a class of nitric oxide-donor drugs [J].
Al-Sa'doni, H ;
Ferro, A .
CLINICAL SCIENCE, 2000, 98 (05) :507-520
[3]   More lipophilic dialkyldiamine-based diazeniumdiolates: Synthesis, characterization, and application in preparing thromboresistant nitric oxide release polymeric coatings [J].
Batchelor, MM ;
Reoma, SL ;
Fleser, PS ;
Nuthakki, VK ;
Callahan, RE ;
Shanley, CJ ;
Politis, JK ;
Elmore, J ;
Merz, SI ;
Meyerhoff, ME .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (24) :5153-5161
[4]   Phase inversion dynamics of PLGA solutions related to drug delivery - Part II. The role of solution thermodynamics and bath-side mass transfer [J].
Brodbeck, KJ ;
DesNoyer, JR ;
McHugh, AJ .
JOURNAL OF CONTROLLED RELEASE, 1999, 62 (03) :333-344
[5]   Platelets at work in primary hemostasis [J].
Broos, Katleen ;
Feys, Hendrik B. ;
De Meyer, Simon F. ;
Vanhoorelbeke, Karen ;
Deckmyn, Hans .
BLOOD REVIEWS, 2011, 25 (04) :155-167
[6]  
de M.M., 2010, J BIOMED MATER RES B, V93, P416
[7]  
DEBELDER AJ, 1994, CARDIOVASC RES, V28, P691
[8]  
Dunn R.L., 1990, U.S. Patent, Patent No. [US patent no. 4,938,763, 4938763, 4,938,763]
[9]   cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action [J].
Francis, Sharron H. ;
Busch, Jennifer L. ;
Corbin, Jackie D. .
PHARMACOLOGICAL REVIEWS, 2010, 62 (03) :525-563
[10]   S-nitrosation/Denitrosation in Cardiovascular Pathologies: Facts and Concepts for the Rational Design of S-nitrosothiols [J].
Gaucher, Caroline ;
Boudier, Ariane ;
Dahboul, Fatima ;
Parent, Marianne ;
Leroy, Pierre .
CURRENT PHARMACEUTICAL DESIGN, 2013, 19 (03) :458-472
1234