Synergistic Cytotoxicity of Human Breast Cancer Cells by a Novel Nano- Particle Based Delivery of Ceramide With Paclitaxel and/or Doxorubicin

摘要

Current chemotherapeutic delivery systems are toxic due drug hydrophobicity. Long circulating polymeric nanoparticles (NPs) are efficient in encapsulating hydrophobic drugs and can provide high loading capacity, controlled release, and compatibility with little toxicity. The use of amphiphilic copolymers provides high solubilization and better drug stability in vivo. Our studies are focused on small nano carrier systems that utilize amphiphilic biodegradable polymers and interact with cellular targets. The use of PEO-Poly(beta-Amino Ester) (PBAE) Nanoparticles to encapsulate paclitaxel was successful with high loading dose and provided pH dependent release and demonstrated cytotoxicity on human breast cancer cells in comparison to control nanoparticles with no encapsulated drug. Our goal is to quantitate the effects of PBAE nanoparticle system and to expand its potential to other drugs such as doxorubicin and ceramide for its efficacies in breast cancer. Our experimentation is focused on the deduction of a formulation of a combination therapy with a delivery system that is practical, reliable and reproducible.