School of Pharmacy and Biomedical Science, Curtin University, Bentley 6102, Australia; Curtin Health Innovation Research Institute, Bentley 6102, Australia.
School of Pharmacy and Biomedical Science, Curtin University, Bentley 6102, Australia; Curtin Health Innovation Research Institute, Bentley 6102, Australia.
Int J Pharm. 2018 Feb 15;537(1-2):223-244. doi: 10.1016/j.ijpharm.2017.12.036. Epub 2017 Dec 26.
Diabetes mellitus is a chronic metabolic health disease affecting the homeostasis of blood sugar levels. However, subcutaneous injection of insulin can lead to patient non-compliance, discomfort, pain and local infection. Sub-micron sized drug delivery systems have gained attention in oral delivery of insulin for diabetes treatment. In most of the recent literature, the terms "microparticles" and "nanoparticle" refer to particles where the dimensions of the particle are measured in micrometers and nanometers respectively. For instance, insulin-loaded particles are defined as microparticles with size larger than 1 μm by most of the research groups. The size difference between nanoparticles and microparticles proffers numerous effects on the drug loading efficiency, aggregation, permeability across the biological membranes, cell entry and tissue retention. For instance, microparticulate drug delivery systems have demonstrated a number of advantages including protective effect against enzymatic degradation, enhancement of peptide stability, site-specific and controlled drug release. Compared to nanoparticulate drug delivery systems, microparticulate formulations can facilitate oral absorption of insulin by paracellular, transcellular and lymphatic routes. In this article, we review the current status of microparticles, microcapsules and microspheres for oral administration of insulin. A number of novel techniques including layer-by-layer coating, self-polymerisation of shell, nanocomposite microparticulate drug delivery system seem to be promising for enhancing the oral bioavailability of insulin. This review draws several conclusions for future directions and challenges to be addressed for optimising the properties of microparticulate drug formulations and enhancing their hypoglycaemic effects.
糖尿病是一种影响血糖稳态的慢性代谢性健康疾病。然而，胰岛素的皮下注射会导致患者不依从、不适、疼痛和局部感染。亚微米级药物输送系统在糖尿病治疗的胰岛素口服递送上受到关注。在最近的大多数文献中，“微粒”和“纳米颗粒”这两个术语是指分别以微米和纳米为单位测量的颗粒尺寸。例如，大多数研究小组将载有胰岛素的颗粒定义为尺寸大于 1 µm 的微粒。纳米颗粒和微粒之间的尺寸差异对药物载药效率、聚集、跨生物膜的渗透性、细胞进入和组织保留产生了众多影响。例如，微粒药物输送系统具有许多优点，包括对酶降解的保护作用、增强肽的稳定性、靶向和控制药物释放。与纳米颗粒药物输送系统相比，微粒制剂可以通过细胞旁途径、细胞内途径和淋巴途径促进胰岛素的口服吸收。本文综述了用于胰岛素口服给药的微粒、微囊和微球的现状。一些新的技术，包括层层涂层、壳的自聚合、纳米复合微粒药物输送系统，似乎有望提高胰岛素的口服生物利用度。这篇综述为优化微粒药物制剂的性质和增强其降血糖效果的未来方向和挑战得出了几个结论。
