Walker S A, Kennedy M T, Zasadzinski J A
Department of Chemical Engineering, University of California, Santa Barbara 93106-5080, USA.
Nature. 1997 May 1;387(6628):61-4. doi: 10.1038/387061a0.
Vesicles of lipid bilayers have been investigated as drug-delivery vehicles for almost 20 years. The vesicles' interior space is separated from the surrounding solution because small molecules have only limited permeability through the bilayer. Single-walled (unilamellar) vesicles are made by a variety of non-equilibrium techniques, including mechanical disruption of lamellar phases by sonication or extrusion through filters, or chemical disruption by detergent dialysis or solvent removal. These techniques do not, however, allow the encapsulation of a specific volume, nor can they be used to encapsulate other vesicles. Here we show that molecular-recognition processes mediated by lipophilic receptors and substrates (here the biotin-streptavidin complex) can be used to produce a multicompartmental aggregate of tethered vesicles encapsulated within a large bilayer vesicle. We call these encapsulated aggregates vesosomes. Encapsulation is achieved by unrolling bilayers from cochleate cylinderss which are tethered to the aggregate by biotin-streptavidin coupling. These compartmentalized vesosomes could provide vehicles for multicomponent or multifunctional drug delivery; in particular, the encapsulating membrane could significantly modify permeation properties, or could be used to enhance the biocompatibility of the system.
脂质双层囊泡作为药物递送载体已被研究了近20年。囊泡的内部空间与周围溶液分隔开，因为小分子通过双层的渗透性有限。单壁（单层）囊泡通过多种非平衡技术制备，包括通过超声处理或通过滤器挤压机械破坏层状相，或通过去污剂透析或溶剂去除进行化学破坏。然而，这些技术不允许封装特定体积，也不能用于封装其他囊泡。在这里，我们表明由亲脂性受体和底物（这里是生物素-链霉亲和素复合物）介导的分子识别过程可用于产生包裹在大双层囊泡内的多隔室拴系囊泡聚集体。我们将这些包裹的聚集体称为囊泡体。通过从螺旋卷曲圆柱体展开双层来实现封装，这些圆柱体通过生物素-链霉亲和素偶联拴系到聚集体上。这些分隔的囊泡体可为多组分或多功能药物递送提供载体；特别是，封装膜可显著改变渗透特性，或可用于增强系统的生物相容性。
