Muzykantov Vladimir, Muro Silvia
Professor of Pharmacology, University of Pennsylvania, 3620 Hamilton Walk, 1 John Morgan Building, Philadelphia, PA 19104-6068, USA.
Fischell Department of Bioengineering, University of Maryland, 5115 Plant Sciences Building, College Park, MD 20742.
Int J Transp Phenom. 2011;12(1-2):41-49.
Delivery and effects of therapeutics remain suboptimal. Most drugs do not have affinity to their targets. Biotherapeutics including enzymes and genetic materials require specific sub-cellular addressing not attainable naturally. Endothelium, lining the luminal surface of blood vessels, represents a key therapeutic target in many diseases. Studies in cell culture and animal models revealed that targeted delivery of therapeutics to, into and across endothelium can be achieved using carriers targeted to specific molecules expressed on the surface of the endothelial cells. For example, cell adhesion molecules represent attractive targets for drug delivery. Rational design of the drug delivery systems (e.g., selection of optimal geometry and affinity to specific epitopes) provides an unprecedented level of control of such parameters of drug delivery as pharmacokinetics, circulation in blood, binding to selected endothelial cell phenotypes, anchoring on cell surface or internalization into the endothelium, subsequent intracellular addressing and duration of the effects. We discusse here key aspects of design of endothelium-targeted drug delivery systems with potential for translation into the clinical domain.
治疗药物的递送和效果仍不尽人意。大多数药物对其靶点没有亲和力。包括酶和遗传物质在内的生物治疗药物需要特定的亚细胞定位，而这是自然无法实现的。血管腔表面的内皮是许多疾病中的关键治疗靶点。细胞培养和动物模型研究表明，使用靶向内皮细胞表面特定分子的载体，可以实现治疗药物向内皮、进入内皮以及穿过内皮的靶向递送。例如，细胞粘附分子是药物递送的有吸引力的靶点。合理设计药物递送系统（例如，选择最佳几何形状和对特定表位的亲和力）可对药物递送的药代动力学、血液中的循环、与选定内皮细胞表型的结合、在细胞表面的锚定或内化进入内皮、随后的细胞内定位以及作用持续时间等参数提供前所未有的控制水平。我们在此讨论有潜力转化到临床领域的内皮靶向药物递送系统设计的关键方面。
