Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration.
Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration.
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DOI：
10.1007/s11095-017-2147-x
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发表时间：
2017-06
影响因子：
3.7
通讯作者：
Reza Nejadnik M
中科院分区：
文献类型：
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作者：
El Bialy I;Jiskoot W;Reza Nejadnik M
骨形态发生蛋白（BMPs）在胚胎发育过程中负责骨形成以及骨再生和重塑。BMP，特别是BMP-2和BMP-7的骨诱导作用导致它们在一系列需要干预以实现有效骨再生的难以克服的治疗中的应用。然而，将BMP产品引入市场并非没有多种并发症和副作用的报道。为了优化治疗效果和安全性，人们一直致力于改善BMP的递送，以降低给药剂量，定位蛋白质，并延长其在作用部位的保留时间。这些努力的主要挑战是应当保持蛋白质的稳定性。通过这次审查，我们试图阐明BMP的稳定性如何在制定和交付过程中受到影响。我们首先提供了一个简短的概述目前的立场与BMP产品的并发症经历。然后，我们讨论了与BMP相关的不同递送参数，以及它们对BMP治疗的疗效和安全性的影响。特别是，文献处理BMP的稳定性和它们可能与递送系统的组分的相互作用以及它们对配制过程的条件的敏感性进行了综述。总之，生物工程和生物制药领域的最新发展表明，对制剂/递送条件与生长因子如BMP的稳定性之间的关系的良好理解是安全有效治疗的先决条件。
Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action. A major challenge with these efforts is that the protein stability should be maintained. With this review we attempt to shed light on how the stability of BMPs can be affected in the formulation and delivery processes. We first provide a short overview of the current standing of the complications experienced with BMP products. We then discuss the different delivery parameters studied in association with BMPs, and their influence on the efficacy and safety of BMP treatments. In particular, the literature addressing the stability of BMPs and their possible interactions with components of the delivery system as well as their sensitivity to conditions of the formulation process is reviewed. In summary, recent developments in the fields of bioengineering and biopharmaceuticals suggest that a good understanding of the relationship between the formulation/delivery conditions and the stability of growth factors such as BMPs is a prerequisite for a safe and effective treatment.