Optimization and screening of solid lipid nanoparticle production for gene delivery by factorial design and response surface methodology

Aim: A successful gene therapy requires a delivery system for overcoming various biological barriers. For this, we adapted the factorial design and response surface methodology to cationic solid lipid nanoparticle production process. Methods: Screening optimization of formulations were carried out with 3 factors levels using Box-Behnken Design. Then, nanoparticles physicochemically characterized. Furthermore, optimal SLN formulation is examined in terms complex formation plasmid DNA, its protection potential against nucleases, cytotoxicity profile, storage stability. Results: Response-surface analyses demonstrated that selected quadratic model holds significance particle size zeta potential. The interaction independent variables was statistically determined. Optimization prediction performed obtained second-order polynomial equations. Optimal complexes found be nanosized, positively charged their polydispersity-index values below 0.3 as an indicator being monodispersed.  Cytotoxicity compatible further studies no significant increase observed until day 21 60 polydispersity-index. Conclusion: provides good basis produced developed systematic. Briefly, this could used obtain SLNs desired conditions.