Fabrication of dispersed drug nanocrystals by femtosecond laser ablation in water

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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.