Paclitaxel is a potent antimicrotub

Paclitaxel is a potent antimicrotubule chemotherapeutic agent widely used for clinical treatment of a variety of solid tumors. However, the low solubility of the drug in aqueous medium and the toxic effects of the commercially available formulation, Taxol, has hindered its clinical application. To overcome these paclitaxel-related disadvantages, several drug delivery approaches have been thoroughly investigated. In this context, our research group has developed long-circulating and pHsensitive liposomes containing paclitaxel composed of dioleylphosphatidylethanolamine, cholesterylhemisuccinate and distearoylphosphatidylethanolamine-polyethylene glycol2000, which have shown to be very promising carriers for this taxane. For the destabilization of pH-sensitive liposomal systems and the release of the encapsulated drug in the cytoplasm of tumor cells, the occurrence of a phase transition from a lamellar to a non-lamellar phase of dioleylphosphatidylethanolamine molecules is essential. Two techniques, differential scanning calorimetry and small angle X-ray scattering, were used to investigate the influence of the liposomal components and paclitaxel in the phase transition process of dioleylphosphatidylethanolamine molecules and to evaluate the pH-sensitivity of the formulation under low hydration conditions. The findings clearly evidence the phase transition of dioleylphosphatidylethanolamine molecules in the presence and absence of PTX indicating that the introduction of the drug in the system does not bring damage to the pH-sensitivity of the system, which resulting in liposomedestabilization at low pH regions and encapsulated paclitaxel release preferentially in a desired target tissue. (C) 2016 Elsevier B.V. All rights reserved.

結果 (中文) 1:

紫杉醇是一种强力的抗微管化疗制剂，广泛用于各种实体瘤的临床诊治。然而，这种药物在水介质中的低溶解度和毒性，商业上可用的制订，紫杉醇，阻碍了其临床应用。为克服这些紫杉醇相关的缺点，几种药物交付方法已经被彻底的调查。在这方面，我们的研究小组已经开发了长循环和酸脂质体紫杉醇组成的 dioleylphosphatidylethanolamine、 cholesterylhemisuccinate 和 distearoylphosphatidylethanolamine 聚乙烯 glycol2000，这已证明是非常有前途这紫杉烷的载体。对于不稳定的 pH 敏感脂质体系统和药物释放的封装在肿瘤细胞的细胞质中，从片状到相变非层状相的 dioleylphosphatidylethanolamine 分子发生至关重要。两种技术，示差扫描量热仪和小角 x 射线散射，被用来探讨脂质体组件和紫杉醇中的 dioleylphosphatidylethanolamine 分子相转变过程的影响，评价 pH 敏感性低水化条件下制定。调查结果清楚证据相变的 dioleylphosphatidylethanolamine 分子中的存在和缺乏 PTX 指示系统中药物概论中不会损坏，对系统，由此在低 ph 值区域和封装紫杉醇 liposomedestabilization 优先释放所需的目标组织中的 pH 敏感性。（C） 2016年唯尔 bv 公司保留所有权利。

結果 (中文) 2:

紫杉醇是一种有效的抗微化疗剂广泛地用于临床治疗各种实体瘤。然而，在含水介质和市售制剂，紫杉醇，的毒性作用的药物的溶解度低已经阻碍了它的临床应用。为了克服这些紫杉醇相关的缺点，一些药物输送的方法已经被彻底调查。在这方面，我们的研究小组开发了长循环和含有dioleylphosphatidylethanolamine，cholesterylhemisuccinate和二硬脂酰 - 聚glycol2000，已显示出对于此紫杉烷非常有前途的载体组成的紫杉醇pHsensitive脂质体。对pH敏感的脂质体系统的不稳定和包封药物在肿瘤细胞的细胞质中的释放，从层状到dioleylphosphatidylethanolamine分子的非层状相的相变的发生是至关重要的。两种技术，差示扫描量热法和小角度X射线散射，被用来研究脂质体成分的dioleylphosphatidylethanolamine分子的相变过程的影响，紫杉醇，并评价所述制剂的低水合的条件下的pH敏感性。该结果清楚证据在存在和不存在的PTX dioleylphosphatidylethanolamine分子指示在系统中引入的药物不会带来损害的系统，其中，导致liposomedestabilization在低pH区域的pH敏感性和封装的相变紫杉醇释放优先在期望的目标组织。版权所有（C）2016年爱思唯尔BV所有权利。

結果 (中文) 3:

紫杉醇是一种强效的抗微管药物广泛用于多种实体肿瘤的临床治疗。然而，药物在水介质中的溶解度较低和市售制剂的毒性作用，阻碍了其临床应用。为了克服这些紫杉醇相关的缺点，一些药物输送的方法已被彻底调查。在这样的背景下，我们的研究小组已经开发了长循环脂质体的组成和pH敏感dioleylphosphatidylethanolamine紫杉醇，cholesterylhemisuccinate和二硬脂酰磷脂酰乙醇胺聚乙烯glycol2000，已证明是非常有前途的载体这紫杉烷。对pH敏感的脂质体系统和封装的药物在肿瘤细胞内释放的不稳定，从层状相过渡到一个dioleylphosphatidylethanolamine分子非层状相的出现是必不可少的。两种技术，差示扫描量热法和X射线小角散射，用于研究分子在dioleylphosphatidylethanolamine相变过程和脂质体成分和紫杉醇对低水化条件下制定的pH敏感性的影响。结果清楚的证据表明，PTX系统中药物的引入并不造成系统的pH敏感性不存在dioleylphosphatidylethanolamine分子的相变，导致liposomedestabilization在低pH值区域和包裹紫杉醇的释放优先目标组织。（C）2016 Elsevier公司保留所有权利。