Introduction: Cancer is one of the most widespread diseases worldwide, with chemotherapy as a common treatment, though often limited by severe side effects and multidrug resistance (MDR). Nanocarrier system with co-delivery of drugs can overcome these side effects by reducing toxicity and enabling combination therapy. Methods: In this study, solid lipid nanoparticles (SLNs) were developed for delivering methotrexate (MTX) and silymarin (SYM) using the microemulsion method, followed by sonication, and optimization via a QbD approach. Optimized SLNs were characterized for compatibility, morphology, particle size, entrapment efficiency, drug release, permeability, anticancer activity, and stability. Results: FTIR confirmed the compatibility of SLN components. DSC and XRD confirmed drug encapsulation and reduced crystallinity, while a small particle size (100-200 nm) provided a favourable morphology for targeting via enhanced permeation and retention. Entrapment efficiencies were observed as 92 % (MTX) and 89 % (SYM). In vitro drug release showed a biphasic profile over 12 h, with an initial burst release followed by sustained release. The surface morphology of SLNs was spherical and uniform, as confirmed by FE-SEM. The IC50 value for MTX-SYM-SLNs was significantly lower than that of pure SYM and MTX. SLNs effectively reduced MCF-7 cell viability, with an IC50 of 390 µg/ml. SLNs were observed to be stable. Discussion: SLNs showed nanosize high entrapment, enhanced cytotoxicity, and sustained release for improved delivery. Conclusion: The co-delivery of MTX and SYM via SLNs presents enhanced cytotoxic effect, which may be attributed to improved cellular uptake and synergistic anticancer activity
Sabale et al. (Fri,) studied this question.