Design and evaluation of erucic acid-phytosphingosine structured cationic nanoemulsions as a plasmid DNA delivery system against breast cancer cells

This study is focused on the preparation and characterization of erucic acid (EA) and phytosphingosine (PS) containing cationic nanoemulsions (NEs) for plasmid DNA (pDNA) delivery. Repurposing of cationic agents guided us to PS, previously used for enhanced interaction with negatively charged surfaces. It was reported that EA might act anti-tumoral on C6 glioma, melanoma, neuroblastoma, and glioblastoma. However, there is only one study about mixed oleic acid-EA liposomes. This gap attracted our interest in the possible synergistic effects of PS and EA on MDA-MB-231 and MCF-7 breast cancer cells. Three cationic NEs (NE 1, NE 2, and NE 3) were prepared and characterized in terms of droplet size (DS), polydispersity index (PDI), and zeta potential (ZP) before and after complexation with pDNA, long-term stability, SDS release, cytotoxicity, and transfection studies. The cationic NEs had DSs of <200 nm, PDIs <0.3, and ZPs > +30 mV. Long-term stability studies revealed that NE 2 and NE 3 were stable. NE 1-pDNA had appropriate particle properties. NE 2 reduced the viability of MDA-MB-231 cells to 11% and of MCF-7 cells to 13% and resulted in the highest number of transfected cells. To sum up, NE 2 containing PS and EA is appropriate for delivering pDNA.