Abstract

Oral delivery of insulin-loaded therapeutics is challenging due to the extreme pH condition, enzymatic degradation, and limited permeation in the gastrointestinal (GI) tract. Nanoparticles can overcome various GI barriers and improve the oral bioavailability of insulin. Although a number of novel strategies have been reported to optimise the orally administered nano-formulation, its clinical translation remains unachievable. Animal studies are essential to establish the protective effect, transit behaviour, retention time, mucoadhesiveness degree, absorption mechanism and distribution of nanoparticle in the GI tract. In this review, we examine various instrumentations, such as Ussing chamber, fluorescence microscope, TEM, CLSM, that are available for investigating the ex vivo intestinal absorption and mucoadhesive capability of insulin-loaded nanoparticles. More importantly, a comprehensive understanding and evaluation of in vivo animal studies are crucial to clarify the physiological properties of insulin nanoparticles. In addition, the biocompatibility of nanoparticle is a critical prerequisite for short-term and long-term use of drug formulation. The success of oral nanomedicine should improve the bioavailability of insulin and elicit no damage to internal organs. Lastly, we reviewed the current status of animal assays, including mucoadhesiveness study, biocompatibility (integrity of intestinal mucosa, histological analysis, oxidative stress, physical symptoms), biodistribution (fluorescence imaging, SPECT) and in vivo efficacy study, for the evaluation of orally administered insulin-loaded nanoparticles in pre-clinical stage.

摘要

由于极端的 pH 值条件、酶促降解和胃肠 (GI) 道中的渗透受限，胰岛素负载疗法的口服给药具有挑战性。纳米颗粒可以克服各种胃肠道障碍，提高胰岛素的口服生物利用度。尽管已经报道了许多新策略来优化口服纳米制剂，但其临床转化仍然无法实现。动物研究对于确定纳米颗粒在胃肠道中的保护作用、转运行为、保留时间、粘膜粘附程度、吸收机制和分布至关重要。在这篇综述中，我们检查了各种仪器，如 Ussing 室、荧光显微镜、TEM、CLSM，可用于研究离体 i载有胰岛素的纳米颗粒的肠道吸收和粘膜粘附能力。更重要的是，对体内动物研究的全面理解和评估对于阐明胰岛素纳米颗粒的生理特性至关重要。此外，纳米颗粒的生物相容性是药物制剂短期和长期使用的关键先决条件。口服纳米药物的成功应该会提高胰岛素的生物利用度，并且不会对内脏造成伤害。最后，我们回顾了动物试验的现状，包括粘膜粘附性研究、生物相容性（肠粘膜完整性、组织学分析、氧化应激、身体症状）、生物分布（荧光成像、SPECT）和体内 功效研究，用于在临床前阶段评估口服胰岛素负载纳米颗粒。