Mesoporous silica nanospheres as nanocarriers for poorly soluble drug itraconazole with high loading capacity and enhanced bioavailability

Abstract

Abstract The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. The poor water solubility often leads to low bioavailability and therapy efficacy of oral administration. Herein, take itraconazole (ITZ), a poorly soluble antifungal agent, as a model drug, we demonstrate a general strategy that nano-amorphous formulation of ITZ with mesoporous silica nanospheres (MSNs) as nanocarriers can result in great enhancement of both the ITZ loading and releasing performance. We find that the sphere diameters and specific surface areas of MSNs have the potential in influencing the amorphous condition of ITZ, further affecting the ITZ loading and releasing behavior. The results indicate that the MSNs with diameter of around 50 nm can load high content (≥37.5 wt%) of ITZ with pure amorphous state, which results in almost 100% in vitro releasing (in simulated gastric fluid) and great enhancement of in vivo bioavailability (1.5 fold greater than that of commercial product Sporanox). Our nano-amorphous strategy for poorly soluble drugs with MSNs as nanocarriers would show great promising in the enhancement of bioavailability and therapy efficacy for oral administration of drugs with poor water solubility.