Nanomedicine & Drug Delivery Systems Group, iMed, Faculty of Pharmacy of the University of Lisbon, Av. Prof Gama Pinto, 1649-003 Lisbon, Portugal.
Adv Drug Deliv Rev. 2009 Nov 12;61(13):1220-31. doi: 10.1016/j.addr.2009.06.003. Epub 2009 Aug 12.
Since the early 1990s polymer-protein conjugates (included PEGylated enzymes and cytokines), polymeric drugs and polymeric sequestrants have been entering the market as innovative polymer-based therapeutics. Initially these products were most frequently developed as novel anticancer agents; indeed they can be considered first generation "nanomedicines". More recently, a much broader range of life-threatening and debilitating diseases (e.g. viral infections, arthritis, multiple sclerosis and hormone abnormalities) have been targeted via intravenous (i.v.), subcutaneous (s.c.) or oral routes of administration. Given the increasing novelty of polymeric materials proposed for development as second-generation polymer therapeutics (with increasing complexity of conjugate composition), and the growing debate as to the safety of nanomedicines per se, the need for evolution of an appropriate regulatory framework is at the forefront of the scientific discussion. The adequacy of the current tests and models used to define safety are also constantly being reviewed. Here we describe the current status and future challenges in relation to these issues.
自 20 世纪 90 年代初以来，聚合物-蛋白质缀合物（包括聚乙二醇化酶和细胞因子）、聚合物药物和聚合物螯合剂作为创新的基于聚合物的治疗剂已经进入市场。最初，这些产品主要作为新型抗癌药物开发；事实上，它们可以被认为是第一代“纳米药物”。最近，更广泛的危及生命和使人虚弱的疾病（例如病毒感染、关节炎、多发性硬化症和激素异常）已经通过静脉（i.v.）、皮下（s.c.）或口服途径进行了靶向治疗。鉴于拟开发为第二代聚合物治疗剂的聚合物材料的新颖性不断增加（缀合物组成的复杂性不断增加），以及纳米药物本身的安全性的争议不断增加，因此需要发展一个适当的监管框架是科学讨论的前沿。目前用于定义安全性的测试和模型的充分性也在不断审查中。在这里，我们描述了与这些问题相关的现状和未来挑战。
