Fabrication of dispersed drug nanocrystals by femtosecond laser ablation in water

许多强效药物的临床应用往往受到其低水溶性的影响。虽然据报道，目前正在研究的药物中约有10%存在与溶解度相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，越来越多的努力是针对研制这种水不溶性药物配方的简单而普遍的技术。已经证明，纳米化有利于注射水溶性差的药物，并有利于增加口服给药后的溶出率。拟议的项目将旨在研究使用最近引进的飞秒激光烧蚀方法在液体中制造药物纳米晶体。与传统的纳米制造方法相比，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浓度的表面活性剂轻松快速地合成纳米颗粒。这能够解决或显著减少与毒性有关的问题和风险。该方法的可行性将在几种模型疏水药物上进行研究，包括紫杉醇（细胞抑制剂）、依托泊苷（囊胞抑制剂）和非诺贝特（脂质调节剂）。用紫杉醇进行的初步试验表明，可以生产药物纳米晶体（500纳米），没有重大化学降解的迹象。这个项目的成功实施可能会转化为改善一些疾病的药物治疗，如癌症和传染病。提出的方法可能允许面临溶解度问题的候选药物的快速临床前评估。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.