Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345C, 2800 Kgs. Lyngby, Denmark.
J Control Release. 2017 Dec 28;268:57-71. doi: 10.1016/j.jconrel.2017.09.025. Epub 2017 Sep 19.
Biopharmaceuticals are increasingly important for patients and the pharmaceutical industry due to their ability to treat and, in some cases, even cure chronic and potentially life-threatening diseases. Most biopharmaceuticals are administered by injection, but intensive focus on development of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals primarily with examples on insulin.
由于生物制药能够治疗某些慢性和潜在威胁生命的疾病，甚至可以治愈这些疾病，因此对于患者和制药行业来说，生物制药越来越重要。大多数生物制药都是通过注射给药，但人们高度关注开发用于生物制药口服给药的系统，这可能会产生新的治疗方式，以提高患者的顺应性并降低产品成本。在临床前开发阶段，使用实验动物模型对于评估新配方设计至关重要。一般来说，生物制药的口服生物利用度仅为几个百分点，因此必须非常谨慎地选择动物模型和实验设置。尽管有许多研究评估了小分子药物口服给药的动物模型，但仍非常需要更多关于这个主题的知识和关注。本文重点介绍和讨论了目前使用最广泛的动物模型和实验设置的优缺点。此外，本文还探讨了麻醉和采样方法对评估生物制药口服给药的药物输送系统的影响，主要以胰岛素为例。
