The critical role of didodecyldimethylammonium bromide on physico-chemical, technological and biological properties of NLC

• DDAB-coated NLC of 150 nm can be prepared by the PIT method.
• Positively charged NLC ensures the sustained and prolonged FA release.
• DDAB increases the lipids order, thus enhancing the NLC physical stability.
• DDAB-coated NLC are able to reduce the viability of human glioblastoma cancer cells.
• DDAB improves the NLC uptake into U87MG glioblastoma cancer cells.

Exploiting the experimental factorial design and the potentiality of Turbiscan AG Station, we developed and characterized unmodified and DDAB-coated NLC prepared by a low energy organic solvent free phase inversion temperature technique. A 22 full factorial experimental design was developed in order to study the effects of two independent variables (DDAB and ferulic acid) and their interaction on mean particle size and zeta potential values. The factorial planning was validated by ANOVA analysis; the correspondence between the predicted values of size and zeta and those measured experimentally confirmed the validity of the design and the equation applied for its resolution. The DDAB-coated NLC were significantly affected in their physico-chemical properties by the presence of DDAB, as showed by the results of the experimental design. The coated NLC showed higher physical stability with no particles aggregation compared to the unmodified NLC, as demonstrated by Turbiscan® AGS measurements. X-ray diffraction, Raman spectroscopy and Cryo-TEM images allowed us to assert that DDAB plays a critical role in increasing the lipids structural order with a consequent enhancement of the NLC physical stability. Furthermore, the results of the in vitro biological studies allow the revisiting of the role of DDAB to the benefit of glioblastoma treatment, due to its efficacy in increasing the NLC uptake and reducing the viability of human glioblastoma cancer cells (U87MG).

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