Volodkin Dmitry, Arntz Youri, Schaaf Pierre, Moehwald Helmuth, Voegel Jean-Claude, Ball Vincent
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 595, 11 rue Humann, 67085 Strasbourg Cedex, France.
Institut Charles Sadron (ICS), Centre National de la Recherche Scientifique, Unité Propre 22, 6 rue Boussingault, 67083 Strasbourg Cedex, France.
Soft Matter. 2007 Dec 11;4(1):122-130. doi: 10.1039/b713563g.
The design of new quasi-2D biocompatible films able to release a drug in a controlled manner through the application of physical stimuli is of outstanding interest in biomaterials science. Herein, construction of composite nanofilms with multiple strata of stabilized large unilamellar liposomes is developed. The film has a multilayered architecture formed by the layer-by-layer (LbL) technique utilising two biocompatible polyelectrolytes, hyaluronic acid and poly-l-lysine (HA and PLL), onto which phospholipid liposome "interlayers" are adsorbed and subsequently embedded by further polyelectrolyte adsorption. First of all the morphology of the film surface is characterised and compared to the morphology obtained for a film containing the same polyelectrolytes but stiff polystyrene (PS) latex particles instead of the soft phospholipid vesicles. Both morphologies appear to be similar suggesting that the embedded vesicles keep their spherical shape. As a second step, it has been shown that carboxyfluorescein (CF) encapsulated in the vesicles remains inside without sustained release at room temperature indicating that the liposomes stay intact upon LbL immobilization. A substantial fraction (about 70%) of the vesicles absorbed onto the polyelectrolyte film are desorbed upon further polyelectrolyte adsorption to reach the embedded state. Hence to achieve high loading of the film, multiple vesicle depositions have to be performed. It is shown that the total number of deposited vesicles on the film is proportional to the number m of vesicle deposition steps (up to m = 3). The encapsulated dye can be released in a controlled manner by a temperature increase above the main phase transition temperature of the lipid mixture used to prepare the vesicles. Release kinetics is faster for film-entrapped vesicles than for those in solution due to destabilization of the lipidic bilayer by the polyelectrolyte environment. The developed composite films represent a new surface biocoating able to preserve, in native state, or to release in a controlled way, surface immobilized materials under external stimuli.
设计能够通过施加物理刺激以可控方式释放药物的新型准二维生物相容性薄膜,是生物材料科学中备受关注的课题。在此,开发了具有多层稳定大单层脂质体的复合纳米薄膜。该薄膜具有通过层层(LbL)技术形成的多层结构,利用两种生物相容性聚电解质,透明质酸和聚-L-赖氨酸(HA和PLL),在其上吸附磷脂脂质体“中间层”,随后通过进一步的聚电解质吸附将其嵌入。首先,对薄膜表面的形态进行表征,并与含有相同聚电解质但用硬聚苯乙烯(PS)乳胶颗粒而非软磷脂囊泡的薄膜所获得的形态进行比较。两种形态似乎相似,表明嵌入的囊泡保持其球形形状。第二步,已表明封装在囊泡中的羧基荧光素(CF)在室温下保持在内部而无持续释放,这表明脂质体在LbL固定化后保持完整。吸附在聚电解质薄膜上的大部分囊泡(约70%)在进一步的聚电解质吸附后解吸以达到嵌入状态。因此,为了实现薄膜的高负载,必须进行多次囊泡沉积。结果表明,薄膜上沉积的囊泡总数与囊泡沉积步骤的数量m成正比(直至m = 3)。通过将温度升高到用于制备囊泡的脂质混合物的主相变温度以上,可以以可控方式释放封装的染料。由于聚电解质环境使脂质双层不稳定,薄膜包裹的囊泡的释放动力学比溶液中的囊泡更快。所开发的复合薄膜代表了一种新型表面生物涂层,能够在外部刺激下以天然状态保存或可控方式释放表面固定的材料。