Formulation and delivery of proteins and peptides
Formulation and delivery of proteins and peptides
复制标题
蛋白质和肽的配制和输送
DOI：
10.1021/bk-1994-0567
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发表时间：
1994
影响因子：
3.7
通讯作者：
R. Langer
中科院分区：
文献类型：
--
作者：
J. Cleland;R. Langer
大多数肽类和蛋白类药物的成功依赖于将生物活性形式递送到作用部位。在设计和开发配方以实现这一目标时，配方科学家必须考虑药物的临床适应症、药代动力学、毒性和物理化学稳定性。开发稳定的配方是每一种新的蛋白质或肽治疗的必要步骤。应系统地分析降解途径及其对稳定性的影响，并必须平衡相互竞争的降解率，以达到尽可能最稳定的配方。还应考虑几种给药途径，今后发展新的配方可能会扩大潜在选择的数目。每种给药途径的配方可能是独特的，因此有特殊的要求。在贮存制剂的情况下，有许多潜在的基质，每一个都有不同的特征，影响其与药物的相互作用及其在体内的行为。制剂特性对药物的体内稳定性以及药代动力学和药效学有很大的影响。结合最近的实例，详细讨论了配方的优化、运输路线、仓库系统的设计以及理化稳定性与体内行为之间的关系。对于包括核酸（DNA载体和反义RNA）在内的新的生物技术衍生药物，要实现商业化，必须在整个开发过程的早期阶段考虑药物配方设计和开发所涉及的所有问题。
The success of most peptide and protein drugs is dependent upon the delivery of the biologically active form to the site of action. In the design and development of formulations to achieve this goal, the formulation scientist must consider the clinical indication, pharmacokinetics, toxicity, and physicochemical stability of the drug. The development of a stable formulation is a necessary step for each new protein or peptide therapeutic. The degradation pathways and their impact on stability should be systematically analyzed and competing degradation rates must be balanced to arrive at the most stable formulation possible. Several routes of administration should also be considered and future development of new formulations may expand the number of potential options. Formulations for each route of administration may be unique and, therefore, have special requirements. In the case of depot formulations, there are many potential matrices, each of which has distinct characteristics that affect its interactions with the drug and its behaviorin vivo. The formulation characteristics may have a dramatic impact on thein vivostability of the drug as well as the pharmacokinetics and pharmacodynamics. The optimization of formulations, the routes of delivery, the design of depot systems, and the correlation between physicochemical stability andin vivobehavior are discussed in detail with recent examples. For new biotechnology-derived drugs including nucleic acids (DNA vectors and antisense RNA) to reach commercialization, all of the issues involved in the design and development of a drug formulation must be considered at an early stage of the overall development process.