Abstract
Aim: To perform a parallel comparison of key parameters affecting the safety and efficiency of lipid-based nanovectors (i.e., complexing headgroups, composition and preparation method). Materials & methods: Various cationic and ionizable headgroups were screened for formulating lipoplexes with GFP-plasmid DNA. Ethanol injection and microfluidics were used to prepare nanoparticles with GFP-plasmid DNA complexed on the surface or within the interior of lipid bilayers. Results: Lipoplexes composed of sphingomyelin 102 exhibited the highest transfection efficiency given their higher cellular uptake in BRAF inhibitor-resistant melanoma cells. Lipid nanoparticlesdemonstrated acceptable transfection efficiency and high spheroid penetration while protecting plasmid DNA under simulated physiological conditions. Conclusion: Selecting the right complexing lipid and preparation method is critical for developing lipid nanocarriers to treat intractable diseases.
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