Fabrication of dispersed drug nanocrystals by femtosecond laser ablation in water

水中飞秒激光烧蚀制备分散药物纳米晶体

• 批准号: 350554-2008
• 负责人: Meunier, Michel
• 金额: $ 5.25万
• 依托单位: École Polytechnique de Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=459213
• 关键词: Fabrication; dispersed; drug; nanocrystals; femtosecond

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.

许多强效药物的临床使用常常因其低水溶性而受到影响。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，而新发现的药物中预计有 40% 的水溶性较差。因此，越来越多的努力致力于开发简单但通用的技术来配制此类水不溶性药物。已经证明，纳米化有利于水溶性差的药物的注射，并有利地提高其口服给药后的溶出率。拟议的项目旨在研究使用最近推出的液体中飞秒激光烧蚀方法来制造药物纳米晶体。与传统纳米制造方法相比，基于激光烧蚀的方法的主要优点是可以在清洁、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粒子。这能够解决或显着减少与毒性相关的问题和风险。将在几种模型疏水性药物上研究所提出的方法的可行性，包括紫杉醇（细胞抑制剂）、依托泊苷（细胞抑制剂）和非诺贝特（脂质调节剂）。用紫杉醇进行的初步测试表明，可以生产药物纳米晶体（500 nm），并且没有重大化学降解的迹象。该项目的成功实施可能会转化为针对癌症和传染病等多种疾病的药物治疗的改进。所提出的方法可以允许对面临溶解度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示对该技术感兴趣。