Wang Yancai, Miao Xiaoqing, Sun Lin, Song Ju, Bi Chao, Yang Xiao, Zheng Ying
Institute of Chinese Medical Sciences, University of Macau, 3/F, Rm 204A, Block 3, Av. Padre Tomás Pereira, S.J. Taipa, Macao SAR, China.
Curr Pharm Des. 2014;20(3):454-73. doi: 10.2174/13816128113199990403.
A surprisingly large proportion of new chemical entities (NCE) is emerging from the drug discovery pipeline, and many active components extracted from herbal medicines are water insoluble, which represents a great challenge for their development. Nanosuspensions, which are submicron colloidal dispersions of pure drug particles that are stabilised by a small percentage of the excipients, could dramatically enhance the saturated solubility, dissolution rate and adhesion of drug particles to cell membranes. Nanosuspensions are the most suitable for drugs that require high dosing or have limited administrative volume. After 20 years of development, several oral products and one injectable product are commercially available. The aim of this review is to fill the gap between rational formulation designs and the in vivo performance of poorly water-soluble drug nanosuspensions. Specifically, this review will correlate characteristics of nanosuspension formulations, including drug property, particle size, crystallinity, stabiliser and surface property, with their transport, pharmacokinetics, bioactivity and toxicity after delivery by different administration routes. The elucidation of the mechanisms of targeted drug delivery, cellular transport and internalisation of nanosuspensions are also reviewed to interpret the in vivo performance of these nanosuspensions. Moreover, the recent application of nanosuspensions for poorly water-soluble herbal medicines is highlighted.
新药研发流程中涌现出的新化学实体（NCE）比例高得出奇，并且许多从草药中提取的活性成分难溶于水，这对其开发而言是巨大挑战。纳米混悬液是由少量辅料稳定的纯药物颗粒的亚微米胶体分散体，可显著提高药物颗粒的饱和溶解度、溶解速率以及与细胞膜的黏附性。纳米混悬液最适用于需要高剂量给药或给药体积受限的药物。经过20年的发展，已有几种口服产品和一种注射产品上市。本综述的目的是填补难溶性药物纳米混悬液合理剂型设计与体内性能之间的空白。具体而言，本综述将纳米混悬液剂型的特性（包括药物性质、粒径、结晶度、稳定剂和表面性质）与其通过不同给药途径给药后的转运、药代动力学、生物活性和毒性联系起来。还综述了纳米混悬液靶向给药、细胞转运和内化机制的阐释，以解读这些纳米混悬液的体内性能。此外，还重点介绍了纳米混悬液在难溶性草药中的最新应用。
