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Optimization and screening of solid lipid nanoparticle production for gene delivery by factorial design and response surface methodology
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Optimization and screening of solid lipid nanoparticle production for gene delivery by factorial design and response surface methodology
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Journal Article
Optimization and screening of solid lipid nanoparticle production for gene delivery by factorial design and response surface methodology
2021
Overview
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 the cationic solid lipid nanoparticle
production process.
Methods: Screening and optimization of formulations were carried out with factorial design with 3 factors and
3 levels using Box-Behnken Design. Then, solid lipid nanoparticles were physicochemically characterized.
Furthermore, optimal SLN formulation is examined in terms of complex formation with plasmid DNA, its
protection potential against nucleases, cytotoxicity profile, and storage stability.
Results: Response-surface analyses demonstrated that the selected quadratic model holds significance for
particle size and zeta potential. The interaction of independent variables was statistically determined.
Optimization and prediction were performed using obtained second-order polynomial equations. Optimal
formulation and complexes were found to be nanosized, positively charged and their polydispersity-index
values below 0.3 as an indicator of being monodispersed. Cytotoxicity of the optimal formulation is
compatible for further studies and no significant increase was observed in particle size until day 21 and until
day 60 for polydispersity-index.
Conclusion: Optimal formulation provides a good basis as a gene delivery system was produced with
developed systematic. Briefly, this methodology could be used to obtain SLNs with desired conditions.
Publisher
Prof. Dr. Hayrettin Öztürk,Experimental Biomedical Research
Subject
