Development and evaluation of a novel nanoparticulate delivery system of arsenic sulfides

Abstract

Realgar (As2S2) and orpiment (As2S3) have long been used as folk medicines to treat various malignant diseases. Because of the intrinsic water-insolubility of realgar and orpiment, it is very difficult to formulate both compounds. In this study, reduced sized realgar and orpiment powders were successfully prepared by using cryo-grinding technique. Significantly increased bioavailability of the corresponding reduced sized realgar and orpiment powders was found in rats after oral administration by comparing the urinary recoveries of the compounds. Further studies showed that the respective realgar and orpiment nanosuspension caused effective inhibition of proliferation of the test gynecological cancer cell lines partially through induction of apoptosis. Realgar and orpiment nanosuspensions were also shown to induce significant alterations of some cancer related genes in our preliminary microarray study. Furthermore, our preliminary toxicity study indicated that realgar and orpiment are genotoxic, as both induce urinary 8-hydroxy-2b -deoxyguanosine, a biomarker for oxidative DNA damage.