Improved brain delivery of vincristine using dextran sulfate complex solid lipid nanoparticles: optimization and in vivo evaluation.

Vincristine (VC) sulfate, a freely water-soluble cytotoxic agent was incorporated into cetyl palmitate solid lipid nanoparticles (SLNs) with the aid of dextran sodium sulfate (DS), a poly anion, using a microemulsion method. The manufacturing process was optimized using response surface methodology (Box-Behnken design). SLNs were characterized for size, zeta potential, morphology, crystallinity, and release behavior. The drug encapsulation efficiency reached up to 93% and release study revealed sustained drug release. SLN formulation showed comparable cytotoxic effect in comparison to VC sulfate solution against the MDA-MB-231 cells. The in vivo studies following injection to rat revealed higher plasma and tissue concentrations and longer drug mean residence times compared to VC solution. Using cumarin-6 as a model drug, it was shown that drug delivery to the brain was enhanced close to five times using SLNs prepared in this study compared to free cumarin-6. It can be concluded that complexes of cetyl palmitate SLNs with DS could produce high VC-loaded SLNs suitable for delivery of anticancer drugs to brain tumors.