Enhanced Anticancer Efficiency of Curcumin Co-Loaded Lawsone Solid Lipid Nanoparticles Against MCF-7 Breast Cancer Cell Lines: Optimization by Statistical JMP Software-Based Experimental Approach.

Abstract

The present study highlighted enhancing the therapeutic effectiveness of curcumin (CUR) co-loaded lawsone (LS) through a solid lipid nanoparticles (SLNs)-based delivery system. The cetyl palmitate (CP), polyethylene glycol 400 (PEG), and probe sonication time (PS) were considered as independent variables whereas particle size and % entrapment efficiency (EE) were selected as dependent variables. The CUR-LS-SLN was developed by hot emulsification followed by probe sonication. A 2³ factorial design was utilized in formulation development using JMP software version 17. Notably, the particle size and %EE of all the formulations were about 500 nm and greater than 75%, respectively. The zeta potential value was found to be -46.8 mV. From leverage plots significant and sensitive factors on particle size and %EE were identified. Contour plots led to the identification of an optimized formula whereby maintaining CP at 100 mg, PEG 400 at 6 mL, and PS at 10 min the desired particle size and %EE was achieved. TEM studies indicated the spherical shape of the particles. MTT assays of Michigan Cancer Foundation-7 (MCF-7) cells showed enhanced efficacy and greater cell inhibition of CUR-LS-SLN and combining both drugs using nanocarriers gave superior inhibition as compared with using either of the drugs evident from IC₅₀ values of 3.7, 9.4, and 2.5 μM, respectively, for CUR, LS, and CUR-LS-SLN. The cells in the combination mostly had irregular cell walls and cell shrinkage was noted and greater cell reduction was also seen. It was found that the enhanced cytotoxicity effect of MCF-7 cells on the developed formulation was attributed to the drug's synergistic actions, more efficient nanocarrier internalizations, and sustained drug release from the formulation. Stability studies indicated that the optimized SLN was stable for 6 months.