Sala M, Locher F, Bonvallet M, Agusti G, Elaissari A, Fessi H
University of Lyon, University Claude Bernard Lyon-1, CNRS, LAGEP UMR 5007, 43 bd. du 11 Nov.1918, F-69622, Villeurbanne, France.
Hospices Civils de Lyon, Pharmacie Centrale, Laboratoire de Contrôle, 57, Rue Francisque Darcieux, 69563, Saint Genis Laval, France.
Pharm Res. 2017 Sep;34(9):1908-1924. doi: 10.1007/s11095-017-2201-8. Epub 2017 Jun 19.
Herein, we detail a promising strategy of nanovesicle preparation based on control of phospholipid self-assembly: the Double Solvent Displacement. A systematic study was conducted and diclofenac as drug model encapsulated. In vitro skin studies were carried out to identify better formulation for dermal/transdermal delivery.
This method consists in two solvent displacements. The first one, made in a free water environment, has allowed triggering a phospholipid pre-organization. The second one, based on the diffusion into an aqueous phase has led to liposome formation.
Homogeneous liposomes were obtained with a size close to 100 nm and a negative zeta potential around -40 mV. After incorporation of acid diclofenac, we obtained nanoliposomes with a size between 101 ± 45 and 133 ± 66 nm, a zeta potential between 34 ± 2 and 49 ± 3 mV, and the encapsulation efficiency (EE%) was between 58 ± 3 and 87 ± 5%. In vitro permeation studies showed that formulation with higher EE% dispayed the higher transdermal passage (18,4% of the applied dose) especially targeting dermis and beyond.
Our results suggest that our diclofenac loaded lipid vesicles have significant potential as transdermal skin drug delivery system. Here, we produced cost effective lipid nanovesicles in a merely manner according to a process easily transposable to industrial scale. Graphical Abstract ᅟ.
在此，我们详细介绍一种基于控制磷脂自组装的纳米囊泡制备的有前景的策略：双溶剂置换法。进行了系统研究，并将双氯芬酸作为药物模型进行包封。开展了体外皮肤研究以确定用于真皮/透皮给药的更佳制剂。
该方法包括两次溶剂置换。第一次在自由水环境中进行，可引发磷脂的预组装。第二次基于向水相的扩散导致脂质体形成。
获得了尺寸接近100 nm且zeta电位约为 -40 mV的均匀脂质体。掺入双氯芬酸后，我们得到了尺寸在101±45至133±66 nm之间、zeta电位在34±2至49±3 mV之间且包封率（EE%）在58±3至87±5%之间的纳米脂质体。体外渗透研究表明，具有较高EE%的制剂显示出较高的透皮通过率（占给药剂量的18.4%），尤其靶向真皮及更深层。
我们的结果表明，我们负载双氯芬酸的脂质囊泡作为透皮皮肤给药系统具有巨大潜力。在此，我们以一种简单的方式生产了具有成本效益的脂质纳米囊泡，其制备过程易于转化为工业规模。图形摘要ᅟ。
