Rosebrugh Bldg, Toronto, ON M5S 3G9
Room: RS 211
The hydrophobicity of many small molecule drugs limits their water solubility. It has been
recently discovered that ~25% of these drugs spontaneously aggregate into amorphous, nanosized particles when their concentration exceeds the critical aggregation concentration. These colloidal drug aggregates produce false positives in drug screens by non-specifically adsorbing and sequestering enzymes. At the same time, the colloidal drug aggregates result in false negatives in cell-based assays due to reduced (if any) cell membrane penetration, leading to a lower intracellular drug concentration and subsequent loss of effectiveness.
While traditionally viewed as a nuisance, we hypothesized that colloidal drug aggregates could be useful as vehicles for drug delivery due to their drug-rich composition and small size. In particle-based formulations, the surface of the particle impacts how it behaves in a physiological environment and ultimately its biological fate. Therefore, we investigated the use of non-ionic surfactants to improve the stability of colloids under physiological conditions. Specifically, we found that surfactants prevent flocculation and growth of the colloids when exposed to salt solutions. The results of this work give further insight on how the physical properties of colloidal drug aggregates affect their behaviour in physiological conditions.