There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of epidermal growth factor receptor (EGFR) inhibitor and doxorubicin (Dox) targeting EGFR signaling applicable for the treatment of triple negative breast cancer and non-small cell lung cancer. To realize this nanoparticle design, EGFR inhibitor complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(L-lactide)-block-polyethylene glycol (PLA-<i>b</i>-PEG) and with an encapsulation efficiency of ~90%. The nanoparticle system exhibited a desired sequential release of EGFR inhibitor followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate fourfold and threefold increases in anti-cancer efficacy compared to a control group of Dox-PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential <i>in vivo</i> applicability by non-invasive fluorescent imaging.

Sequential co-delivery of EGFR inhibitor and doxorubicin for targeted combination chemotherapy

256th National Meeting (2018)

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