Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380494, Chile; Advanced Center for Chronic Diseases (ACCDiS), Santiago 8380494, Chile; Pharmaceutical Biomaterial Research Group, Department of Health Sciences, Luleå University of Technology, Luleå 97187, Sweden.
UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Curr Opin Pharmacol. 2017 Oct;36:22-28. doi: 10.1016/j.coph.2017.07.011. Epub 2017 Aug 8.
Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics. It is likely however that printed film designs with lower molecular weight stable biotech payloads including lipophilic glucagon-like 1 (GLP-1) agonists and macrocycles with long half-lives will generate greater efficacy than was achieved to date for insulin.
大分子（生物制剂）经颊给药对研究人员来说是一个巨大的挑战。虽然已经有几种利基小分子产品被批准为简单的喷雾剂、片剂和口腔薄膜，但将现有技术简单地应用于生物制剂并不适用。胰岛素的颊部给药已经通过两种方法进入临床试验：用渗透增强剂进行口腔喷雾的肽，以及在可溶解薄膜中嵌入金纳米粒子。然而，这两种方法都没有获得 FDA 的批准，可能是由于疗效不佳、剂型中肽的载药量不足以及药代动力学和药效学的个体内变异性较大。然而，具有较低分子量稳定生物技术有效载荷的印刷薄膜设计，包括亲脂性胰高血糖素样肽-1 (GLP-1) 激动剂和半衰期较长的大环，可能会比目前胰岛素的疗效更好。
