Carter K C, Puig-Sellart M
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
Curr Pharm Des. 2016;22(22):3324-31. doi: 10.2174/1381612822666160418121700.
Treatment by the pulmonary route can be used for drugs that act locally in the lungs (e.g. lung cancer) or non-invasive administration of drugs that act systemically (e.g. diabetes). The potential of using drug delivery systems (DDS) formed from non-ionic surfactants or natural products for pulmonary drug delivery are reviewed.
The effectiveness of each DDS depends on it ability to not only entrap the relevant drug and alter its bio distribution, but also its ability to withstand the physical stresses during nebulization and for the nebuliser to produce aerosol particles with the size for deposition in the appropriate part of the lungs. Different methods must be used to prepare nanoparticles (NP) using non-ionic surfactants, or biocompatible polymers from natural proteins or sugars, and the aqueous solubility of the drug also influences the manufacture method.
NP produced using non-ionic surfactants, proteins such as collagen, albumin or gluten, and polysaccharides such as chitosan, hyaluronate, cellulose, carrageenans, alginate or starch has successfully delivered different types of drugs given by the pulmonary route. Drug entrapment efficiency depends on the DDS constituents and the manufacture method used. Large scale manufacture of DDS from natural products is technically challenging but changing from batch manufacture to continuous manufacturing processes has addressed some of these issues, and inclusion of a spray drying step has been beneficial in some cases.
DDS for lung delivery can be produced using natural products but identifying a cost effective manufacture method may be challenging and the impact of using different type of nebulisers on the physiochemical characteristics of the aerosolised formulation should be an essential part of formulation development. This would ensure that some of the development work e.g. stability studies do not have to be repeated as they will identify if a carrier to protect the DDS from the physical trauma caused by nebulisation.
肺部给药途径可用于作用于肺部局部的药物(如肺癌治疗)或全身性作用药物的非侵入性给药(如糖尿病治疗)。本文综述了使用由非离子表面活性剂或天然产物形成的药物递送系统(DDS)进行肺部药物递送的潜力。
每种DDS的有效性不仅取决于其包封相关药物并改变其生物分布的能力,还取决于其在雾化过程中承受物理应力的能力以及雾化器产生适合沉积在肺部适当部位的气溶胶颗粒的能力。必须使用不同的方法来制备纳米颗粒(NP),使用非离子表面活性剂或由天然蛋白质或糖类制成的生物相容性聚合物,药物的水溶性也会影响制造方法。
使用非离子表面活性剂、胶原蛋白、白蛋白或麸质等蛋白质以及壳聚糖、透明质酸、纤维素、角叉菜胶、藻酸盐或淀粉等多糖制备的NP已成功通过肺部途径递送了不同类型的药物。药物包封效率取决于DDS成分和所使用的制造方法。从天然产物大规模制造DDS在技术上具有挑战性,但从分批制造转变为连续制造工艺已经解决了其中一些问题,并且在某些情况下加入喷雾干燥步骤是有益的。
可使用天然产物生产用于肺部递送的DDS,但确定具有成本效益的制造方法可能具有挑战性,并且使用不同类型雾化器对雾化制剂理化特性的影响应成为制剂开发的重要组成部分。这将确保一些开发工作(如稳定性研究)不必重复,因为它们将确定是否有载体来保护DDS免受雾化引起的物理损伤。