This paper describes a novel method

This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean' like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release. (C) 2016 Elsevier B.V. All rights reserved.

結果 (中文) 1:

本文介绍了一种新方法提高难溶性 （亲脂性） 模型药物 asulacrine (ASL) 脂质体的药物残留。ASL 加载在水相中的脂质体和老化条件下和载药量水平对药物保留的影响等进行了本研究建立体外生物相关药物释放试验。用示差扫描量热 (DSC) 和冷冻透射电镜 (冷冻-TEM) 研究了内脂质体药物的现状。药代动力学及静脉耐受性配方同时研究了兔耳缘静脉通过后一小时静脉滴注。老化过程中葡萄糖的存在被发现是至关重要的以加速药物沉淀，从而稳定脂质体膜的高药量 (8.9%超过 4.5 %w / w) 作为先决条件。虽然没有药物晶体被检测到，dsc 分析表明较低的阶段过渡峰值在葡萄糖协助老年 ASL-脂质体，指示磷脂和糖的互动。冷冻-透射电镜显示更多咖啡豆像药物沉淀在 ASL 脂质体岁在葡萄糖溶液中。兔，这些脂质体给上升到 1.9 倍长半衰期比新鲜的脂质体，观察无静脉刺激。诱导和糖在老化稳定脂质体核心药物降水提供一个容易的方法来提高脂质体中的药物残留。这项研究还强调了生物相关性预测体内药物释放的体外释放方法的重要性。（C） 2016年唯尔 bv 公司保留所有权利。

結果 (中文) 3:

本文介绍了一种提高难溶性药物保留在脂质体的新方法（亲油）的模型药物asulacrine（ASL）。ASL是装在脂质体的水相和老化条件和药物负荷水平对药物保留的效果是通过体外的生物相关的药物释放试验，本研究建立的研究。内脂质体药物的现状采用差示扫描量热法研究（DSC）和冷冻透射电子显微镜（冷冻透射电镜）。通过耳静脉的一小时静脉滴注，同时研究了该制剂在家兔体内的药动学和静脉耐受性。在老化过程中葡萄糖的存在被认为是加速药物的沉淀，高载药脂质体稳定的关键（8.9%超过4.5% W / W）为前提。虽然没有药物晶体进行检测，分析显示低相变峰在葡萄糖辅助老年ASL脂质体，说明磷脂与糖的相互作用。的Cryo-TEM透露更多的“咖啡豆”喜欢在ASL脂质体在葡萄糖溶液中老年药物沉淀。在兔子中，这些脂质体产生了一个1.9倍的半衰期比新鲜的脂质体，没有观察到静脉刺激。在糖的存在下，在脂质体核心的诱导和稳定药物沉淀提供了一个简单的方法，以提高药物保留在脂质体。这项研究还强调了生物相关性的体外释放方法来预测体内药物释放的重要性。（C）2016 Elsevier公司保留所有权利。