Review physical and chemical aspects of stabilization of compounds in silk.
Review physical and chemical aspects of stabilization of compounds in silk.
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DOI：
10.1002/bip.22026
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发表时间：
2012-06
期刊：
影响因子：
2.9
通讯作者：
Kaplan DL
中科院分区：
文献类型：
--
作者：
Pritchard EM;Dennis PB;Omenetto F;Naik RR;Kaplan DL
稳定小分子和蛋白质的挑战已经引起了相当大的兴趣。小分子的生物活性可能由于化学修饰而丧失，而蛋白质活性可能由于化学或结构降解而丧失，例如大分子构象或聚集的变化。在这些情况下，需要稳定化以保持治疗和生物活性功效和安全性。除了用于治疗应用外，稳定小分子和蛋白质的策略还可应用于工业过程、诊断以及食品和化妆品等消费品。传统上，治疗药物制剂的努力集中在产品制备和储存期间保持稳定性。然而，随着对包封、组织工程和控释药物递送系统领域的兴趣日益增长，新的稳定化挑战正在得到解决;感兴趣的化合物或蛋白质必须在以下过程中稳定化：（1）蛋白质或小分子负载载体的制造，（2）装置储存，和（3）体外或体内预期释放需要的持续时间。本文综述了生物材料（包括组织工程支架和药物释放系统）制备、储存和体内植入过程中小分子和蛋白质化合物降解的常见机制。我们还回顾了基于聚合物的稳定方法的物理和化学方面，特别关注丝素蛋白生物材料的稳定特性。
The challenge of stabilization of small molecules and proteins has received considerable interest. The biological activity of small molecules can be lost as a consequence of chemical modifications, while protein activity may be lost due to chemical or structural degradation, such as a change in macromolecular conformation or aggregation. In these cases stabilization is required to preserve therapeutic and bioactivity efficacy and safety. In addition to use in therapeutic applications, strategies to stabilize small molecules and proteins also have applications in industrial processes, diagnostics, and consumer products like food and cosmetics. Traditionally, therapeutic drug formulation efforts have focused on maintaining stability during product preparation and storage. However, with growing interest in the fields of encapsulation, tissue engineering and controlled release drug delivery systems, new stabilization challenges are being addressed; the compounds or protein of interest must be stabilized during: (1) fabrication of the protein or small molecule loaded carrier, (2) device storage, and (3) for the duration of intended release needs in vitro or in vivo. We review common mechanisms of compound degradation for small molecules and proteins during biomaterial preparation (including tissue engineering scaffolds and drug delivery systems), storage and in vivo implantation. We also review the physical and chemical aspects of polymer-based stabilization approaches, with a particular focus on the stabilizing properties of silk fibroin biomaterials.