Fabrication of dispersed drug nanocrystals by femtosecond laser ablation in water

许多强效药物的临床使用往往因其低水溶性而受到影响。虽然据报道，目前正在研究的药物中约有10%存在与溶解性有关的生物利用度问题，但预计新发现的药物中有40%的水溶性较差。因此，越来越多的努力旨在开发简单但通用的技术来配制这种不溶于水的药物。研究表明，纳米化有利于难溶药物的注射，并有利于提高口服后的溶出度。这项拟议的项目旨在研究利用最近引入的飞秒激光在液体中烧蚀的方法来制造药物纳米晶体。与传统的纳米加工方法相比，基于激光烧蚀的方法的主要优点是在清洁、无污染的环境中以最低的表面活性物质浓度轻松、快速地合成纳米颗粒。这使得能够解决或显著减少与毒性相关的问题和风险。将在包括紫杉醇(细胞抑制剂)、依托泊苷(膀胱剂)和非诺贝特(血脂调节剂)在内的几种模型疏水药物上研究所提出的方法的可行性。对紫杉醇进行的初步测试表明，可以生产出药物纳米晶(500 Nm)，没有主要化学降解的迹象。这一项目的成功完成可能转化为对癌症和传染病等一些病理疾病的药物疗法的改进。建议的方法可能允许对面临溶解性问题的候选药物进行快速临床前评估。一家加拿大制药公司已经表达了对这项技术的兴趣。

The clinical use of many potent drugs is often being compromised by their low water solubility. While it is reported that about 10% of the drugs currently under investigation present solubility-related bioavailability problems, 40% of the newly discovered drugs are expected to be poorly water-soluble. Increasing efforts are hence directed at developing simple yet universal technologies for the formulation of such water-insoluble drugs. It has been demonstrated that nanonization facilitates the injection of poorly-water soluble drugs and favourably increases their dissolution rate following oral administration. The proposed project will be aimed at investigating the use of the recently introduced method of femtosecond laser ablation in liquids to fabricate drug nanocrystals. The main advantage of the laser ablation-based approach compared to conventional nanofabrication methods is the facile and fast synthesis of nanoparticles in clean, contamination-free environment with minimal concentration of surface active agents. This enables to solve or significantly reduce toxicity-related problems and risks.The feasibility of the proposed approach will be investigated on several model hydrophobic drugs including paclitaxel (cytostatic agent), etoposide (cystotatic agent) and fenofibrate (lipid regulating agent). Preliminary tests conducted with paclitaxel revealed that drug nanocrystals (500 nm) could be produced with no signs of major chemical degradation. The successful fulfillment of this project may translate into improved drug therapies for a number of pathologies such as cancer and infectious diseases. The proposed approach may allow the rapid preclinical evaluation of candidate drugs that face solubility problems. A Canadian pharmaceutical company has already expressed interest in the technology.