Lewis Andrew L, Illum Lisbeth
Critical Pharmaceuticals Limited, BioCity Nottingham, Pennyfoot Street, Nottingham NGI IGF, UK.
Ther Deliv. 2010 Sep;1(3):457-79. doi: 10.4155/tde.10.17.
Proteins constitute an increasing proportion of the drugs in development. The barriers to their entry into the blood stream and rapid clearance means that they often have to be injected several times a day, affecting patient compliance. This paper reviews the major technologies enabling the development of injectable sustained-release products and formulation strategies to maintain protein integrity and modify release rates. Whilst many injectable sustained-release products are on the market, these are all delivering small molecular weight drugs and peptides. This is due to the manufacturing processes that denature and degrade the proteins upon encapsulation and release into the body. Formulation strategies are discussed and a number of new technologies reviewed that are able to overcome the issues with conventional manufacturing processes. The reliance of many processes on organic solvents has prevented their application to the development of injectable sustained release protein products. The development of entirely solvent free and aqueous methods of manufacture of these products has meant that numerous sustained-release protein products are close to reaching the market.
在研发中的药物里，蛋白质所占的比例越来越大。蛋白质进入血流存在障碍且清除速度快，这意味着它们常常必须每天注射数次，从而影响患者的依从性。本文综述了促成可注射缓释产品研发的主要技术以及维持蛋白质完整性和调节释放速率的制剂策略。虽然市面上有许多可注射缓释产品，但这些产品都在递送小分子药物和肽。这是因为制造工艺会在包封和释放到体内时使蛋白质变性和降解。文中讨论了制剂策略，并综述了一些能够克服传统制造工艺问题的新技术。许多工艺对有机溶剂的依赖阻碍了它们应用于可注射缓释蛋白质产品的研发。这些产品完全无溶剂且采用水性制造方法的发展意味着众多缓释蛋白质产品已接近上市。
