Yang Sixing, Yuan Weien, Jin Tuo
Shanghai Jiao Tong University, China.
Expert Opin Drug Deliv. 2009 Oct;6(10):1123-33. doi: 10.1517/17425240903156374.
This review is aimed at providing critical comments on selected approaches to formulating protein drugs into particulate forms feasible as practical pharmaceutical dosage forms. From a practical point of view, the need to formulate protein therapeutics into particulate forms includes inhalation and sustained-release delivery proteins, stabilizing and incorporating proteins into tissue engineering scaffolds and medical devices, as well as protecting and targeting protein therapeutics in an in vivo environment. For either of the applications, a common challenge is that proteins are easily denatured during particle-forming processes in which water-oil or water-air interfaces, multivalent ions or polyelectrolytes, strong shear stress and/or reactive crosslinking agents are often involved. Moreover, methods to protect proteins during the particle-forming processes must not compromise their pharmaceutical objectives, such as encapsulation efficiency, burst-free controlled release and storage convenience. Although numerous methods have been reported to formulate proteins into particulate systems, few of them meet the criteria above. To stimulate critical and interactive readings of the vast and booming information, the authors also provide their analysis regarding the feasibility of the formulation strategies summarized in this review.
本综述旨在对将蛋白质药物制成可行的实用药物剂型颗粒形式的选定方法提出批判性意见。从实际角度来看，将蛋白质治疗剂制成颗粒形式的需求包括吸入和缓释递送蛋白质、将蛋白质稳定并整合到组织工程支架和医疗设备中，以及在体内环境中保护和靶向蛋白质治疗剂。对于任何一种应用，一个共同的挑战是蛋白质在颗粒形成过程中容易变性，在这些过程中通常涉及水-油或水-气界面、多价离子或聚电解质、强剪切应力和/或反应性交联剂。此外，在颗粒形成过程中保护蛋白质的方法绝不能损害其药学目标，如包封效率、无突释控释和储存便利性。尽管已经报道了许多将蛋白质制成颗粒系统的方法，但很少有方法符合上述标准。为了激发对大量且不断涌现的信息进行批判性和互动性阅读，作者还提供了他们对本综述中总结的制剂策略可行性的分析。
