Heidel Jeremy D, Schluep Thomas
Calando Pharmaceuticals, Inc., 225 South Lake Avenue, Suite 300, Pasadena, CA 91101, USA.
J Drug Deliv. 2012;2012:262731. doi: 10.1155/2012/262731. Epub 2012 Feb 2.
Nanoparticles are being widely explored as potential therapeutics for numerous applications in medicine and have been shown to significantly improve the circulation, biodistribution, efficacy, and safety profiles of multiple classes of drugs. One leading class of nanoparticles involves the use of linear, cyclodextrin-containing polymers (CDPs). As is discussed in this paper, CDPs can incorporate therapeutic payloads into nanoparticles via covalent attachment of prodrug/drug molecules to the polymer (the basis of the Cyclosert platform) or by noncovalent inclusion of cationic CDPs to anionic, nucleic acid payloads (the basis of the RONDEL platform). For each of these two approaches, we review the relevant molecular architecture and its rationale, discuss the physicochemical and biological properties of these nanoparticles, and detail the progress of leading drug candidates for each that have achieved clinical evaluation. Finally, we look ahead to potential future directions of investigation and product candidates based upon this technology.
纳米颗粒作为医学领域众多应用的潜在治疗手段正被广泛研究,并且已显示出能显著改善多种药物的循环、生物分布、疗效和安全性。一类主要的纳米颗粒涉及使用含线性环糊精的聚合物(CDP)。如本文所讨论的,CDP可通过将前药/药物分子共价连接到聚合物上(Cyclosert平台的基础)或将阳离子CDP非共价包合到阴离子核酸负载物上(RONDEL平台的基础),将治疗有效载荷整合到纳米颗粒中。对于这两种方法中的每一种,我们回顾相关的分子结构及其原理,讨论这些纳米颗粒的物理化学和生物学性质,并详细介绍已进入临床评估阶段的每种方法的主要候选药物的进展。最后,我们展望基于该技术的潜在未来研究方向和候选产品。