Development of Macromolecule‐Based Drug Delivery System Nanoparticles for Lung Cancer Therapy

Abstract

Lung cancer is the second most common cancer and the leading cause of cancer mortality in the U.S. For decades, many chemotherapeutic agents have been used in clinical settings, however, issues regarding low therapeutic index and acquired resistance to drugs (e.g. Cisplatin and Doxorubicin) have arisen. In this way, the use of macromolecules and lipids as the drug carriers, as targeting ligands or as therapeutic agents has had great impact in the development of drug delivery system (DDS) nanomedicines to improve these drawbacks. Herein we developed DDS using biocompatible macromolecules, i.e. serum albumin (BSA), lysozyme (Lyz) and methyl-β-cyclodextrin (mβCD) as drug carriers and linoleic acid (LinOA) as the coating. The cytotoxic agents, doxorubicin (DOX), berberine (Ber) and curcumin (Curc) were conjugated to each carrier using oil in water in oil (O/W/O)-like emulsion system followed by heat and ultrasonication. DDS have three drugs types incorporated in the carrier structure by non-covalent interactions. To characterize the incorporation of the drugs, fluorimetric measurements were done. The sizes of the DDS were determined ~ 100-1000 nm using dynamic light scattering. All the developed DDS demonstrated cytotoxic patterns in the μM range after 24h incubated with lung cancer cells (A549). These DDS have potential to minimize drug systemic toxicity and increase drug bioavailability. Future experiments will be performed to determine the impact to reduce multidrug resistance.