Nanoparticle-based Drug Delivery Platforms for Enhanced Chemoradiation of Colorectal Cancer

A. DuRoss, M. Metcalf, J. Rosch, M. Neufeld, C. Sun
Oregon State University, College of Pharmacy,
United States

Keywords: drug delivery, chemoradiation, nanoparticle, pluronic, PARP, colon cancer


Multimodality cancer therapies often offer improved tumor cell kill over individual treatments, such as surgery, radiation, or chemotherapy alone. However, these combined approaches also carry increased unwanted toxicities for the patient. In an effort to reduce these limiting side-effects, nanoparticle drug carriers have been investigated for site specific and controlled release of therapeutic agents. In our previous work, we have developed a variety of polymeric, inorganic, and composite nanomaterials capable of delivering hydrophilic or hydrophobic chemotherapeutic compounds to cancer cells. Here, we present a pluronic-based nanoparticle platform for the delivery of a poly-ADP ribose polymerase (PARP) inhibitor, talazoparib, to colon cells. Formulation of the pluronic micelles by rapid mixing and self-assembly in an aqueous solution were evaluated dynamic light scattering and transmission electron microscopy (TEM). The hydrodynamic size of the drug loaded particles were approximately 24.5 nm and correlated well with that observed by TEM (~20nm). An encapsulation efficiency of 65% for talazoparib in the pluronic nanoparticles was achieved. The resulting nanoparticles were evaluated for efficacy against a colon cancer cell line, CT-26, to assess cytotoxicity in vitro. Preliminary chemoradiation studies were also performed with the free drug in combination with radiation by assessing DNA damage via the