Muzykantov Vladimir R
University of Pennsylvania, Institute for Environmental Medicine and Department of Pharmacology, Philadelphia, 19104-6068, USA.
Expert Opin Drug Deliv. 2005 Sep;2(5):909-26. doi: 10.1517/17425247.2.5.909.
Drug targeting to selected subcellular compartments of the pulmonary endothelium may optimise treatment of many diseases. This paper describes endothelial determinants that are potentially useful for such targeting, including endothelial ectopeptidases, cell adhesion molecules and novel candidates identified by high-throughput methods, as well as the means to achieve optimal subcellular targeting of drugs in the endothelium that have been explored in cell culture and animal studies. Criteria for determining the applicability for targeting include accessibility, specificity, safety and subcellular precision. The effects of endothelial delivery of therapeutic agents, including the effects mediated by the intervention in the function of the target determinants, must be characterised in the context of given pathological conditions.
将药物靶向作用于肺内皮细胞的特定亚细胞区室可能会优化多种疾病的治疗。本文描述了对这种靶向作用可能有用的内皮决定因素,包括内皮外肽酶、细胞粘附分子以及通过高通量方法鉴定的新候选物,以及在细胞培养和动物研究中探索的实现药物在内皮细胞中最佳亚细胞靶向的方法。确定靶向适用性的标准包括可及性、特异性、安全性和亚细胞精准度。治疗剂的内皮递送效应,包括通过干预靶决定因素的功能介导的效应,必须在特定病理条件下进行表征。