Development of serum albumin‐based drug delivery system nanoparticles combining Doxorubicin and a natural triterpene for a synergistic cancer therapy

Abstract

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Cytotoxic drugs are the main therapy against cancer; however, they are frequently associated with severe side-effects related to systemic toxicity and lack of tumor specificity. As consequence, the use of proteins as drug carriers has had great impact in the development of new approaches as drug delivery system (DDS) nanoparticles (NPs). For example, Abraxane®, the first FDA-approved DDS NPs, is composed of serum albumin protein and paclitaxel drug, and has demonstrated higher tumor accumulation, patient toleration, and response rate than the free paclitaxel. Due to this, the aim of this research project is the development of a synergistic DDS NPs using serum albumin (BSA), as the drug's carrier, coupling two cytotoxic drugs: doxorubicin (DOX), and the natural triterpene betulinic acid (BeA). This system BSA[(Dox)(BeA)] was done by using water in oil (W/O)-like emulsion followed by heat and ultrasonication. To characterize the BSA and Dox concentration in the DDS, colorimetric assays were performed. DDS's size was determined ~ 100 nm using dynamic light scattering. All the developed DDS demonstrated a strong IC50 in the μM range after 24h incubated with lung (A549) and resistant-ovarian (A2780-CP20) cancer cells. A complete discussion of the results will be presented. These DDS have potential to minimize drug systemic toxicity and increase drug bioavailability.