Wu Fei, Jin Tuo
School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
AAPS PharmSciTech. 2008;9(4):1218-29. doi: 10.1208/s12249-008-9148-3. Epub 2008 Dec 16.
While the concept of using polymer-based sustained-release delivery systems to maintain therapeutic concentration of protein drugs for extended periods of time has been well accepted for decades, there has not been a single product in this category successfully commercialized to date despite clinical and market demands. To achieve successful systems, technical difficulties ranging from protein denaturing during formulation process and the course of prolonged in vivo release, burst release, and incomplete release, to low encapsulation efficiency and formulation complexity have to be simultaneously resolved. Based on this updated understanding, formulation strategies attempting to address these aspects comprehensively were reported in recent years. This review article (with 134 citations) aims to summarize recent studies addressing the issues above, especially those targeting practical industrial solutions. Formulation strategies representative of three areas, microsphere technology using degradable hydrophobic polymers, microspheres made of water soluble polymers, and hydrophilic in vivo gelling systems will be selected and introduced. To better understand the observations and conclusions from different studies for different systems and proteins, physicochemical basis of the technical challenges and the pros and cons of the corresponding formulation methods will be discussed.
尽管使用基于聚合物的缓释给药系统来长时间维持蛋白质药物的治疗浓度这一概念在过去几十年中已被广泛接受，但尽管有临床和市场需求，该类别的单一产品至今仍未成功商业化。为了实现成功的系统，必须同时解决一系列技术难题，包括制剂过程中以及体内长时间释放过程中的蛋白质变性、突释、释放不完全，以及包封效率低和制剂复杂性高等问题。基于这一更新的认识，近年来报道了一些试图全面解决这些问题的制剂策略。这篇综述文章（引用文献134篇）旨在总结近期针对上述问题的研究，特别是那些针对实际工业解决方案的研究。将选择并介绍代表三个领域的制剂策略，即使用可降解疏水性聚合物的微球技术、由水溶性聚合物制成的微球以及亲水性体内凝胶系统。为了更好地理解不同研究针对不同系统和蛋白质的观察结果和结论，将讨论技术挑战的物理化学基础以及相应制剂方法的优缺点。
