Development of Polymer-Based Nanoparticles for the Reduction of Melittin Toxicity

Melittin is a naturally occurring cytotoxic peptide, derived from a component in the poison of the European honeybee Apis mellifera. Bee venom has been used for the treatment of pain, rheumatoid arthritis, and chronic inflammatory diseases, and its knowns with anti-cancer, anti-microbial, anti-viral peptide, and other pharmacological properties. Melittin is a peptide that has potential in the treatment of various diseases. However, melittin induces pore formation in the cell membrane due to its positive charge and causes cell lysis. To overcome this disadvantage and take advantage of the potential effect of melittin, novel negatively charged PMMA/SPMA was synthesized by RAFT polymerization, and nanoparticles were formed by the nanoprecipitation method. After melittin was complexed with the nanoparticles, the size of the nanoparticles were slightly increased from 223 to 550 nm, whereas the charge of the nanoparticles were increased from -40 to -2.97 mV. Critic micelle concentration (CMC) was 17 mu g/mL and the binding efficiency was determined as 83.45% by measuring the fluorescence density in the supernatants. The cytotoxicity results indicate that the toxicity of melittin (IC50: 2.23 mu M) has been successfully abolished with MEL NPs in Raw 264.7 cells. These nanoparticles have the potential to facilitate the successful and effective utilization of melittin in various treatments, creating potential for its use in diverse therapies.