Novel ST1926 Nanoparticle Drug Formulation Development and Therapeutic Potential in Colorectal Cancer

Abstract

Nanomedicine has gained significant interest over the years as it provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. It is a fast-evolving field that holds promise for the novel development of various therapeutic inventions, particularly in the treatment of cancer. The use of nanoparticle (NP) formulations in drug delivery has been applied to various cancer types and has shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Colorectal cancer (CRC), is among the most common types of cancers diagnosed worldwide. It imposes a health burden as it ranks third in terms of cancer incidence and second in terms of mortality worldwide. CRC results from the accumulation of aberrant genetic and epigenetic alterations within cells of the colon and/or rectum. Despite advances in CRC surgical techniques, chemotherapy, radiotherapy, and targeted therapy, disease resistance remains a major obstacle in the survival of patients, emphasizing the need for novel therapeutic modalities. We have previously shown that the adamantyl retinoid ST1926 displays potent anti-tumor activities in human CRC models. However, ST1926 is limited by its low bioavailability which resulted in it being halted in phase I clinical trials in cancer patients. Therefore, we developed novel ST1926-NPs and assessed their efficacy in CRC models. ST1926 was formulated into NPs using Flash NanoPrecipitation with a drug to polymer to co-stabilizer mass ratio of 1:2:0.2. Dynamic light scattering has shown that the Contin ST1926-NP diameter was 97 nm, with a polydispersity index of 0.206. Using viability, cell cycle, and cell death assays, we showed that ST1926-NPs exhibited potent anti-tumor activities in the human CRC HCT116 cells. In a CRC xenograft model, the tumor volumes of mice treated with ST1926-NP were significantly lower than those of the controls, even at very low concentrations of ST1926 in NPs. In conclusion, our research supports the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC, facilitating its further development in clinical settings.