Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, NJ 07033, United States.
Pharmaceutical Sciences, Merck & Co., Inc., Kenilworth, NJ 07033, United States.
Adv Drug Deliv Rev. 2021 Jul;174:1-29. doi: 10.1016/j.addr.2021.02.007. Epub 2021 Feb 17.
Protein therapeutics carry inherent limitations of membrane impermeability and structural instability, despite their predominant role in the modern pharmaceutical market. Effective formulations are needed to overcome physiological and physicochemical barriers, respectively, for improving bioavailability and stability. Knowledge of membrane affinity, cellular internalization, encapsulation, and release of drug-loaded carrier vehicles uncover the structural basis for designing and optimizing biopharmaceuticals with enhanced delivery efficiency and therapeutic efficacy. Understanding stabilizing and destabilizing interactions between protein drugs and formulation excipients provide fundamental mechanisms for ensuring the stability and quality of biological products. This article reviews the molecular studies of biologics using solution and solid-state NMR spectroscopy on structural attributes pivotal to drug delivery and stability. In-depth investigation of the structure-function relationship of drug delivery systems based on cell-penetrating peptides, lipid nanoparticles and polymeric colloidal, and biophysical and biochemical stability of peptide, protein, monoclonal antibody, and vaccine, as the integrative efforts on drug product design, will be elaborated.
尽管蛋白质疗法在现代制药市场中占据主导地位，但它们仍然存在固有局限性，包括膜通透性和结构不稳定性。为了提高生物利用度和稳定性，需要有效的制剂来克服生理和物理化学屏障。了解载药载体的膜亲和力、细胞内化、包封和释放，可以揭示设计和优化具有增强递药效率和治疗效果的生物制药的结构基础。了解蛋白质药物与制剂辅料之间的稳定和不稳定相互作用，为确保生物制品的稳定性和质量提供了基本机制。本文综述了使用溶液和固态 NMR 光谱学对药物传递和稳定性关键结构属性进行的生物学分子研究。深入研究基于穿透肽、脂质纳米粒和聚合物胶体的药物传递系统的结构-功能关系，以及肽、蛋白质、单克隆抗体和疫苗的生物物理和生化稳定性，这些都是药物产品设计的综合努力。
