纳米晶体技术及其提升水难溶药物药理学功效的研究进展

Advances in nanocrystal technology and its application to improve the pharmacological efficacy for poorly-water soluble drugs

为解决水难溶性药物溶解度低所导致的口服吸收波动大和生物利用度低的问题,近年来相继开发了固体分散体、脂质体、微乳、囊泡、环糊精包合物及药物纳米晶体等新型制剂,其中,药物纳米晶体以其制备工艺简单、载药量高且易于深加工制备成适合多种给药途径的剂型等优点而备受关注。本文介绍了基于bottom-up和top-down技术制备水难溶药物纳米晶体的方法,以及基于纳米晶体开发的混悬剂、片剂和胶囊剂等剂型的特点,重点介绍了这些制剂经口服、注射和肺部吸入等途径给药后在药代动力学、药效学及组织靶向性等方面相对于原料药所具有的优势,并阐述了相关的内在机制。最后,对药物纳米晶体的基础研究与产业化方面存在的问题和解决途径进行了探讨,以使这种新型药物制剂能发挥更好的临床疗效。

In order to solve the problems of erratic drug absorption and low bioavailability after oral administration for poorly-water soluble drugs due to low solubility,a series of novel pharmaceutical dosage forms as solid dispersion,liposome,microemulsion,vesicle,cyclodextrin inclusion complexes and drug nanocrystal have been developed in recent years.Among which drug nanocrystal attracts more attentions for its simpler preparation method,higher drug loading and easier manufacturing technology in the design of dosage forms suitable for different administration routes.In this paper,the nanocrystals of the poorly-water soluble drugs prepared based on bottomup and top-down technologies were introduced.The characteristics and applications of the nanocrystal-based dosage forms as suspension,tablet and capsule were also introduced and carefully evaluated with the focus on their pharmacokinetics,pharmacodynamics and tissue targeted drug distribution after delivery by oral administration,intravenous injection and pulmonary inhalation.The advantages of drug nanocrystals in their therapeutics effects over the bulk drugs were discussed together with the inherent mechanism.Finally,the problems existing in basic research and scaled-up manufacture of drug nanocrystal as well as the possible ways of solution were listed out so as to make the nanocrystal-based preparations exert their maximum therapeutic effect after clinical application.