Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility.
Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility.
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DOI：
10.1007/s43032-021-00576-5
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Herington J
中科院分区：
文献类型：
--
作者：
Hansen CJ;Siricilla S;Boatwright N;Rogers JH;Kumi ME;Herington J
非常需要开发宫缩抑制和子宫收缩药物，以对抗不良的、与分娩相关的孕产妇和胎儿结局。评估新型化合物的保胎和子宫收缩功效的一种广泛使用的方法是等长器官浴收缩试验。不幸的是，水不溶性化合物可能难以使用生理的、基于缓冲液的器官浴测定法进行测试。克服溶解度问题的常见方法包括溶剂变化、共溶、表面活性剂或络合物的使用以及乳化。然而，这些药物递送或制剂的选择可能影响组织功能。因此，本研究的目的是评价常用溶剂、表面活性剂、共溶剂和乳剂在器官浴试验中充分溶解化合物而不影响小鼠子宫肌层收缩性的能力。我们发现，丙酮，乙腈和乙醇的影响最小，而二甲基乙酰胺，乙酸乙酯和异丙醇显示最大的抑制子宫肌层收缩的收缩曲线下的面积分析的基础上。最低浓度的表面活性剂，共溶剂，和人血清白蛋白所需的溶解硝苯地平，目前保胎药物，导致广泛的鼓泡在器官浴测定，排除了它们的使用。最后，我们报告了不含药物的水包油基乳剂没有超出对照（水）的统计学效应，而药物乳剂产生了与自由溶解的药物相同的效力和功效。在线版本包含补充材料，可通过10.1007/s43032 - 021 - 00576 - 5获得。
A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug. The online version contains supplementary material available at 10.1007/s43032-021-00576-5.
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DOI：
10.1016/s1470-0328(03)00051-x
发表时间：
2003-04-01
影响因子：
5.8
作者：
Keirse, MJNC
通讯作者：
Keirse, MJNC
影响因子：
3.3
作者：
BRAAK, K;FREY, HH
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FREY, HH
DOI：
10.1111/j.1748-1716.1977.tb10387.x
发表时间：
1977-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
EK, A;ALM, P;PERSSON, CGA
通讯作者：
PERSSON, CGA
DOI：
10.1016/0002-9378(71)90806-4
发表时间：
1971-01-01
影响因子：
9.8
作者：
HORIGUCHI, T;SUZUKI, K;ADAMSONS, K
通讯作者：
ADAMSONS, K
影响因子：
4.8
作者：
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