Jiang Wenlei, Lionberger Robert, Yu Lawrence X
US Food and Drug Administration, Office of Generic Drugs, 7519 Standish Place, Rockville, MD 20855, USA.
Bioanalysis. 2011 Feb;3(3):333-44. doi: 10.4155/bio.10.204.
One challenge in developing a nanoparticle drug-delivery system is understanding the critical physicochemical properties that may impact its in vivo performance and establishing analytical techniques that can adequately characterize in vitro and in vivo properties. Doxil®/Caelyx®, a PEGylated liposomal doxorubincin (PLD), is one of the leading approved nanoparticle product used in cancer therapy. In this review, we use PLD as an example to illustrate identification of key in vitro and in vivo characteristics. The following characteristics, including liposome composition, state of encapsulated drug, internal environment of liposome, liposome size distribution, lamellarity, grafted polyethylene glycol at the liposome surface, electrical surface potential or charge, and in vitro leakage, are considered critical to demonstrate the supramolecular structure of PLD and ensure consistent drug delivery to cancer tissues. Corresponding analytical techniques are discussed to determine these liposome characteristics. Furthermore, in vivo stability of the PLD can be determined by plasma pharmacokinetics of both free and liposome-encapsulated drug. A better understanding of the critical in vitro and in vivo liposome characteristics together with improvements in analytical technology will enable generic liposome product development and ensure liposome product quality.
开发纳米颗粒药物递送系统面临的一个挑战是了解可能影响其体内性能的关键物理化学性质，并建立能够充分表征体外和体内性质的分析技术。阿霉素脂质体（Doxil®/Caelyx®），一种聚乙二醇化脂质体阿霉素（PLD），是用于癌症治疗的领先获批纳米颗粒产品之一。在本综述中，我们以PLD为例来说明关键体外和体内特性的识别。以下特性，包括脂质体组成、包封药物状态、脂质体内环境、脂质体大小分布、层数、脂质体表面接枝的聚乙二醇、表面电势或电荷以及体外渗漏，被认为对于证明PLD的超分子结构和确保向癌组织一致地递送药物至关重要。讨论了用于确定这些脂质体特性的相应分析技术。此外，PLD的体内稳定性可以通过游离药物和脂质体包封药物的血浆药代动力学来确定。更好地了解关键的体外和体内脂质体特性以及分析技术的改进将有助于通用脂质体产品的开发并确保脂质体产品质量。
