Yakavets Ilya, Lassalle Henri-Pierre, Scheglmann Dietrich, Wiehe Arno, Zorin Vladimir, Bezdetnaya Lina
Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, Campus Sciences, Boulevard des Aiguillette, 54506 Vandoeuvre-lès-Nancy, France.
Research Department, Institut de Cancérologie de Lorraine, 6 Avenue de Bourgogne, 54519 Vandoeuvre-lès-Nancy, France.
Nanomaterials (Basel). 2018 Oct 18;8(10):847. doi: 10.3390/nano8100847.
The main goal of this study was to use hybrid delivery system for effective transportation of temoporfin (-tetrakis(3-hydroxyphenyl)chlorin, mTHPC) to target tissue. We suggested to couple two independent delivery systems (liposomes and inclusion complexes) to achieve drug-in-cyclodextrin-in-liposome (DCL) nanoconstructs. We further optimized the composition of DCLs, aiming to alter in a more favorable way a distribution of temoporfin in tumor tissue. We have prepared DCLs with different compositions varying the concentration of mTHPC and the type of β-cyclodextrin (β-CD) derivatives (Hydroxypropyl-, Methyl- and Trimethyl-β-CD). DCLs were prepared by thin-hydration technique and mTHPC/β-CD complexes were added at hydration step. The size was about 135 nm with the surface charge of (-38 mV). We have demonstrated that DCLs are stable and almost all mTHPC is bound to β-CDs in the inner aqueous liposome core. Among all tested DCLs, trimethyl-β-CD-based DCL demonstrated a homogenous accumulation of mTHPC across tumor spheroid volume, thus supposing optimal mTHPC distribution.
本研究的主要目标是使用混合递送系统将替莫泊芬（-四（3-羟苯基）二氢卟吩，mTHPC）有效地运输到靶组织。我们建议将两种独立的递送系统（脂质体和包合物）结合起来，以实现药物-环糊精-脂质体（DCL）纳米结构。我们进一步优化了DCL的组成，旨在以更有利的方式改变替莫泊芬在肿瘤组织中的分布。我们制备了具有不同组成的DCL，改变了mTHPC的浓度和β-环糊精（β-CD）衍生物（羟丙基-β-CD、甲基-β-CD和三甲基-β-CD）的类型。DCL通过薄膜水化技术制备，在水化步骤中加入mTHPC/β-CD复合物。其尺寸约为135 nm，表面电荷为（-38 mV）。我们已经证明DCL是稳定的，并且几乎所有的mTHPC都与脂质体内水相核心中的β-CD结合。在所有测试的DCL中，基于三甲基-β-CD的DCL在肿瘤球体体积中显示出mTHPC的均匀积累，因此推测其具有最佳的mTHPC分布。
