Development of ivermectin-encapsulated solid lipid nanoparticles as a therapeutic approach against hsp-27 mediated drug resistance in mda-mb- 231 breast cancer cells

Abstract

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype with limited targeted treatment options. Ivermectin (IVM), traditionally used as an antiparasitic agent, has shown growing potential as a repurposed anti-cancer drug due to its ability to induce cell death and inhibit proliferative signaling pathways. To enhance its delivery and therapeutic performance, solid lipid nanoparticles (SLNs) were employed as a drug delivery nanoparticle. IVM-loaded SLNs were prepared using the solvent evaporation method and were characterized for particle size, surface charge, polydispersity index, and in vitro drug release profile. The cytotoxic potential of the formulation was evaluated on the MDA-MB-231 TNBC cell line using MTT assay, with comparisons made against free IVM and blank SLNs and wound healing effect was evaluated by the scratch assay.Further molecular analysis was conducted through RT-PCR to check the expression levels of HSP27, EGFR, apoptosis and EMT markers. The study demonstrated that IVM-SLNs promoted enhanced cytotoxicity at lower concentrations, achieved sustained drug release, and exhibited favorable physicochemical attributes. These results underline the promise of IVMloaded SLNs as a nanotherapeutic strategy for improving the efficacy of ivermectin in breast cancer treatment.