NEPN Northeast Preclinical Network
Nanotechnology is revolutionizing the medical field. The main application areas of nanoparticles include therapeutics, delivery of pharmaceuticals, implanted devices and medical imaging tracers. Nanoparticles behave differently than other similarly-sized particles. The nanomaterial size, surface charge, surface characteristics, shape, architecture, composition and solubility alter the pharmacokinetic, the route of clearance and toxicity. The major organs affected by the administration of the nanoparticles included, but are not limited to, lungs, brain, heart, spleen, kidneys, liver, circulatory systems and lymphatic systems. It is therefore essential to determine the toxicity of nanoparticles prior to its commercialization and its use in humans. The tests required by the regulatory authorities for human testing are expensive (GLP studies). It is important to determine early in development the safety thereof.
The CNBE is a contractual research organization specialized in exploratory non-GLP animal studies. The CNBE has developed a low cost program to explore the toxicity of nanoparticles before moving to expensive and definitive GLP studies. This program is ideal for screening a number of drug candidates to identify the lead compound or to validate batch-to-batch consistency. A difference in size as little as 2 nm may influence the clearance and toxicity. The program developed by the CNBE is based on 1) the determination of the maximal tolerated dose (MTD) on a limited number of female Sprague-Dawley rats (4 per group per dose) and 2) the evaluation of side effects on a cohort of 5 rats per group using three (3) different doses administered at a regimen of once a day for 7 days. Toxicological parameters evaluated were:
The observed results are used to calculate both NOAEL and NOEL ("non-observable adverse effect limit" and "non-observable effect limit") and to establish a safety margin for the tested product. These data will be useful to take a rational decision on a given nanoparticle before investing time and money in its development (abandonment, modification of the nanoparticle or further development).