Evaluation of thermosensitive poloxamer 407 gel systems for the sustained release of estradiol in a fish model
Evaluation of thermosensitive poloxamer 407 gel systems for the sustained release of estradiol in a fish model
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DOI：
10.1016/j.ejpb.2014.08.008
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发表时间：
2014-11-01
影响因子：
4.9
通讯作者：
Mosconi, Gilberto
中科院分区：
文献类型：
--
作者：
Cespi, Marco;Bonacucina, Giulia;Mosconi, Gilberto
本研究的目的是开发和评价一种包含热敏凝胶的递送系统，用于在鱼中持续释放类固醇激素，在单次肌内（i.m.）基于热敏凝胶的控释系统易于制备，成本低，剂型多样性高，已在几种动物中显示出对激素的缓释有效。乙醇介质，能够作为17 β-雌二醇（E2）的缓释载体，已被开发。这种系统能够溶解亲脂性E2，并在养鱼所需的水温（20 ℃）下胶凝。此外，该系统表现出最佳的注射条件下，温度低于15 ℃时，该系统表现为一个低粘度的牛顿液体。注射溶于玉米油的E2和其它不含E2的相关控制系统。结果特别有趣，因为注射E2热敏凝胶制剂的鱼在注射后72小时和96小时显示出比玉米油E2处理的动物显着更高的循环激素水平。此外，热凝胶系统能够维持血浆E2水平约11天。E2的血浆水平的增加也伴随着维持较高的血浆卵黄蛋白原（VTG）的值，从而表明基于热敏聚合物的递送系统可以防止E2的快速肝脏清除，导致金鱼中雌激素受体介导的途径的延长刺激。(C)2014爱思唯尔有限公司版权所有。
The purpose of this study was to develop and evaluate a delivery system comprising a thermosensitive gel for the sustained release of steroidal hormones in fish, over an extended period of time after a single intramuscular (i.m.) injection and for the improved reproductive performance in fish.Controlled delivery systems based on thermosensitive gels are easy to prepare, low cost and high versatility dosage forms, which have been shown to be effective in several animal species for sustained release of hormones.In this work, a thermosensitive gel system based on poloxamer 407 in water: ethanol medium, able to work as a prolonged release carrier for 17 beta-estradiol (E2), has been developed. Such a system was able to solubilize the lipophilic E2 and to gel at the required water temperature for fish rearing (20 degrees C). Moreover, the system exhibited the best injection condition at temperatures below 15 degrees C when the system behaved as a low viscosity Newtonian liquid.The thermosensitive gel system was tested in vivo in the fish model, Carassius auratus, and the results compared with a single i.m. injection of E2 dissolved in corn-oil and other relevant control systems not containing E2. The results were particularly interesting, since fish injected with the E2 thermosensitive gel formulation, showed significantly higher levels of the circulating hormone than corn oil-E2 treated animals at 72 and 96 h after injection. In addition, the thermogel system was able to sustain the plasma level of E2 for about 11 days. The increased plasma levels of E2 were also accompanied by maintained higher values of plasma vitellogenin (VTG), thus suggesting that the thermosensitive polymer based delivery system could prevent rapid hepatic clearance of E2, resulting in prolonged stimulation of estrogen receptor-mediated pathways in goldfish. (C) 2014 Elsevier B.V. All rights reserved.