Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency.
Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency.
复制标题
十二烷基肌酸酯和脂质纳米胶囊：治疗肌酸转运蛋白缺乏的双重策略。
DOI：
10.2217/nnm.13.205
复制
发表时间：
2015
期刊：
影响因子：
5.5
通讯作者：
A. Mabondzo
中科院分区：
文献类型：
--
作者：
Alexandra Trotier;C. Passirani;J. Béjaud;S. Dézard;V. Valayannopoulos;F. Taran;P. de Lonlay;J. Benoit;A. Mabondzo
背景
肌酸转运蛋白 (CT) 缺陷的特点是编码 CT 的基因发生突变，导致细胞膜上肌酸的转运受损。因此，患有这种疾病的患者将受益于补充脑细胞内的肌酸。
目的
我们报告了一种基于使用十二烷基肌酸酯掺入脂质纳米胶囊（LNC）的治疗策略。
材料与方法
使用 Transcutol(®)（Gattefossé SAS，Saint-Priest，法国）将十二烷基肌酸酯掺入 LNC 的壳中。研究了 LNC 中封装的十二烷基肌酸酯与体外基于细胞的血脑屏障模型的相互作用。在 CT 缺陷的病理背景下，还研究了包裹在 LNC 中的十二烷基肌酸酯的进入以及十二烷基肌酸酯在细胞中转化为肌酸的情况。
结果与讨论
我们证明这些 LNC 可以穿过血脑屏障并进入脑内皮细胞。在缺乏功能性 CT 的人成纤维细胞中，全部或部分十二烷基肌酸酯从 LNC 中释放并生物转化为肌酸，从而表明了该策略在此治疗背景下的价值。
BACKGROUND
Creatine transporter (CT) deficiency is characterized by mutations in the gene encoding CT, leading to impaired transport of creatine at the cell membrane. Patients with this disease would thus benefit from replenishment of creatine inside the brain cells.
AIM
We report a therapeutic strategy based on the use of dodecyl creatine ester incorporated into lipid nanocapsules (LNCs).
MATERIALS & METHODS
The dodecyl creatine ester was incorporated in the shells of LNCs using Transcutol(®) (Gattefossé SAS, Saint-Priest, France). The interactions of dodecyl creatine ester encapsulated in LNCs with an in vitro cell-based blood-brain barrier model was studied. The entry of the dodecyl creatine ester encapsulated in LNCs and the conversion of dodecyl creatine ester to creatine in the cells were also studied in the pathological context of CT deficiency.
RESULTS & DISCUSSION
We showed that these LNCs can cross the blood-brain barrier and enter brain endothelial cells. In human fibroblasts lacking functional CT, all or part of the dodecyl creatine ester was released from the LNCs and biotransformed to creatine, thus indicating the value of this strategy in this therapeutic context.