Atypical retinoid ST1926 nanoparticle formulation development and therapeutic potential in colorectal cancer

Title : Atypical retinoid ST1926 nanoparticle formulation development and therapeutic potential in colorectal cancer

Abstract:

Cancer represents a major public health and economic burden, being the second leading cause of death worldwide. Despite recent advances in cancer therapy, anti-cancer drug development remains a challenging field due to several hurdles faced along the process. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability thereby minimizing drug dosage and toxicity. Nanoparticle (NP) formulations in drug delivery have been applied successfully in various cancer models and in the clinic.

We have previously shown that the adamantyl retinoid ST1926 displays potent anti-tumor and apoptotic activities in colorectal cancer in vitro and in vivo models. However, ST1926 is limited by its low bioavailability and increased glucuroconjugation which resulted in it being halted in phase I clinical trials in cancer patients. Therefore, we developed ST1926-NPs and assessed their efficacy in colorectal cancer models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2 providing a stable formulation for one week. Dynamic light scattering has shown that the contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as the naked ST1926 in the human colorectal cancer HCT116 cells, at low micromolar concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a colorectal cancer xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Our research will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in colorectal cancer and its further development in the clinic.

Biography:

Sara Assi is a PhD candidate at the American University of Beirut (AUB) in Lebanon. She graduated with a Bachelor of Science in biology from the Lebanese American University. She then joined AUB to pursue a Master of Science degree in biology. After that, she worked on an interdisciplinary project between the chemical engineering, cell biology, and surgery departments at AUB which motivated her to pursue a PhD in biomedical engineering. She then joined the research group of Dr. Walid Saad and Dr. Nadine Darwiche to work on her PhD project.