Synthesis of Self-Assembled Nanostructured Cisplatin Using the RESS Process

The primary goal of our research is to develop a process to prepare an aqueous dispersion of Cisplatin, an important anticancer drug, with increased solubility and storage stability. In this context, we report the use of a customized RESS process for the synthesis of a novel, amber-colored and viscous aqueous cisplatin solution, an important anticancer drug, which we have denoted as "liquid" cisplatin. Using specialized liquid cell in situ transmission electron microscopy (Liquid in situ TEM) and Raman spectroscopy, we demonstrated that "liquid" cisplatin comprises a bi-modal distribution of a highly solvated network of stable cisplatin nanoclusters in water and exhibited 27 times greater water solubility than standard cisplatin. More importantly, "liquid" cisplatin was stable at ambient conditions for over two years. Extensive analytical characterization of "liquid" cisplatin confirmed that it retained the original chemical identity of cisplatin. Cell viability and apoptosis studies on human lung adenocarcinoma A549 cells provided compelling evidence that "liquid" cisplatin demonstrated a more sustained anticancer effect compared to standard cisplatin. Aqueous cisplatin solubility was increased by 27X in the "liquid" cisplatin medium which retained its bio efficacy over a 2-year period. Our experimental results suggest the possibility of developing non-invasive and highly effective novel cisplatin drug-delivery platforms.