News & Events
Aaron H. Colby, Ph.D.
Posted on January 22, 2016
Date - January 22, 2016
Post-Doctoral Research Fellow
Harvard Medical School, Brigham and
Women’s Hospital & Boston University
“Novel Drug Delivery Systems: pH-Responsive Expansile Nanoparticles & Drug Concentrating Devices as Tools for Treating Cancer”
New treatments and drug delivery strategies are required to treat patients with cancer—the second leading cause of death worldwide. Current chemotherapeutic treatments frequently suffer from poor water solubility, systemic toxicity, poor accumulation within the target tissues and an inability to eradicate all remaining tumor following resection procedures. Nanoparticles (NPs) are extensively investigated as a means to increase drug solubility, alter biodistribution, target specific sites within the body, and minimize drug side effects and, as such, numerous NP formulations are being investigated as drug delivery devices to assist in the treatment and management of cancer. We have developed a pH-responsive expansile nanoparticle (eNP) that can encapsulate the hydrophobic chemotherapeutic agent Paclitaxel (Pax) (a poorly water soluble, yet potent chemotherapeutic agent), and deliver it specifically to the intracellular compartment of tumor cells. Paclitaxel-loaded-eNPs (Pax-eNPs) localize specifically to regions of intraperitoneal (IP) tumors and, once taken up by tumor cells, undergo a conformational change upon exposure to the mildly acidic cellular endosome that results in eNP swelling and intratumoral drug release. In this talk I will describe the synthesis and characterization of the eNP as well as the improved efficacy of Pax-eNPs compared to the standard clinical formulation of Pax (i.e., Pax dissolved in Cremophor EL/Ethanol) and the ability of eNPs to act as intratumoral, intracellular drug concentrating devices. Further investigation of this NP-based drug delivery system will facilitate a greater understanding of the materials and devices used in the delivery of chemotherapeutic agents and may lead to the clinical translation and application of eNPs.