Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide
Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide
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DOI：
10.1016/j.jconrel.2007.04.016
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发表时间：
2007-07-31
影响因子：
10.8
通讯作者：
Kohane, Daniel S.
中科院分区：
文献类型：
--
作者：
Yea, Yoon;Adil, Maroof;Kohane, Daniel S.
腹膜粘连是手术或其他损伤后在腹盆腔内形成的组织连接。它们可能导致严重的医疗并发症。屏障装置和药物已被用于防止粘连形成，取得了好坏参半的成功。我们假设，粘连屏障也提供抗粘连药物，可以解决粘连形成的物理和生理原因。在这里，我们描述了原位交联透明质酸水凝胶（屏障装置）含有糖皮质激素受体激动剂布地奈德。选择布地奈德是因为已知炎症在粘连形成中的作用，选择透明质酸是因为其在腹膜中的已知生物相容性。该系统由两种交叉前体液体组成，使用双管注射器施加，在不到5秒内形成柔性和耐用的水凝胶。我们在兔腹膜粘连形成的严重重复侧壁缺损-盲肠磨损模型中，将该制剂或对照品应用于第二次损伤后的损伤部位。所有盐水处理动物均出现大粘连（中位面积15.4 cm（2））。在用盐水中的布地奈德（中位面积5.0 cm（2））或不含布地奈德的水凝胶（中位面积4.9 cm（2））治疗的动物中，粘连形成和面积略有减轻。在水凝胶中使用布地奈德治疗的动物中，粘连的发生率和面积显著降低（中位面积0.0 cm（2））。在大鼠皮下注射中，与单独的水凝胶相比，水凝胶中的布地奈德减少了炎症。总之，透明质酸水凝胶中的布地奈德易于使用，并且在我们的严重重复损伤模型中预防粘连非常有效。这是一个潜在的有前途的系统，用于术后粘连预防，并表明，屏障装置的有效性可以大大提高并发药物输送。(c)2007 Elsevier B. V.保留所有权利。
Peritoneal adhesions are tissue connections that form within the abdominopelvic cavity following surgery or other injuries. They can cause major medical complications. Barrier devices and pharmacological agents have been used to prevent adhesion formation, with mixed success. We hypothesize that an adhesion barrier which also delivers anti-adhesion drugs can address both physical and physiological causes for adhesion formation. Here, we describe an in situ cross-linking hyaluronan hydrogel (barrier device) containing the glucocorticoid receptor agonist budesonide. Budesonide was chosen because of the known role of inflammation in adhesion formation, hyaluronan because of its known biocompatibility in the peritoneum. The system, consisting of two cross-linkable precursor liquids, was applied using a double-barreled syringe, fort-ning a flexible and durable hydrogel in less than 5 s. We applied this formulation or controls to the injured sites after the second injury in a severe repeat sidewall defect-cecum abrasion model of peritoneal adhesion formation in the rabbit. Large adhesions (median area 15.4 cm(2)) developed in all saline-treated animals. Adhesion formation and area were slightly mitigated in animals treated with budesonide in saline (median area 5.0 cm(2)) or the hydrogel without budesonide (median area 4.9 cm(2)). The incidence and area of adhesions were dramatically reduced in animals treated with budesonide in the hydrogel (median area 0.0 cm(2)). In subcutaneous injections in rats, budesonide in hydrogel reduced inflammation compared to hydrogel alone. In summary, budesonide in a hyaluronan hydrogel is easy to use and highly effective in preventing adhesions in our severe repeated injury model. It is a potentially promising system for post-surgical adhesion prevention, and suggests that the effectiveness of barrier devices can be greatly enhanced by concurrent drug delivery. (c) 2007 Elsevier B.V. All rights reserved.