Fabrication of dispersed drug nanocrystals by femtosecond laser ablation in water

许多有效药物的临床使用经常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%是水溶性差的。因此，越来越多的努力致力于开发用于配制这种水不溶性药物的简单而通用的技术。已经证明，纳米化促进了水溶性差的药物的注射，并且有利地增加了它们在口服给药后的溶出速率。拟议的项目将旨在研究使用最近推出的飞秒激光烧蚀方法在液体中制造药物纳米晶体。与传统的纳米纤维方法相比，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小浓度的表面活性剂容易且快速地合成纳米颗粒。这使得解决或显着降低毒性相关的问题和risk.The可行性的建议的方法将研究几个模型疏水药物，包括紫杉醇（细胞生长抑制剂），依托泊苷（膀胱扩张剂）和非诺贝特（脂质调节剂）。用紫杉醇进行的初步测试显示，可以产生药物纳米晶体（500 nm），而没有主要化学降解的迹象。该项目的成功实施可能会转化为癌症和传染病等多种疾病的药物治疗方法的改进。所提出的方法可以允许快速的临床前评估的候选药物面临的溶解度问题。一家加拿大制药公司已经表示对这项技术感兴趣。

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.