(17h) Sequential Co-Delivery of EGFR Inhibitor and Doxorubicin for Targeted Combination Chemotherapy | AIChE

(17h) Sequential Co-Delivery of EGFR Inhibitor and Doxorubicin for Targeted Combination Chemotherapy


Lee, J. Y. - Presenter, University of Cincinnati
Zhou, Z., University of Cincinnati
Jafari, M., University of Cincinnati
Sequential co-delivery of EGFR inhibitor and doxorubicin for targeted combination chemotherapy

Zilan Zhoua, Mina Jafaria, Joo-Youp Leea,*

a Chemical Engineering Program, Department of Biomedical, Environmental, and Chemical Engineering, University of Cincinnati, Cincinnati, Ohio 45221-0012, U.S.A.

* Corresponding author: Joo-Youp Lee

Tel.: +1 513-566-0018; Fax: +1 413-556-0018

E-mail: joo.lee@uc.edu

Combination therapy holds great promise in enhancing treatment outcomes. To achieve synergistic effects for combination therapy, tumor cells should be exposed to drugs with effective doses at optimal drug ratio. There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving enhanced efficacy. However, due to diverse physicochemical properties of drugs, it is challenging to co-deliver effective doses of drugs to tumor sites at optimal ratio and time delay in drug presentation. In this study, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable to the treatments of triple negative breast cancer. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(L-lactide)-block-polyethylene (PLA-PEG) and with an encapsulation efficiency of ~90%. The nanoparticle system exhibited a desired sequential release of Gi and Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated ~fourfold increase in anti-cancer efficacy compared to a control group of Dox-PLA-PEG conjugate. High tumor accumulations of the nanoparticles were also substantiated for potential in vivo applicability by non-invasive fluorescent imaging.