Experimental factorial design applied to mucoadhesive lipid nanoparticles via multiple emulsion process

Solid lipid nanoparticles (SLNs) produced from multiple emulsions technology theoretically enclose an inner aqueous compartment suitable for hydrophilic biomolecules. This paper reports a 3(3) full factorial design study to optimize SLNs formulations for hydrophilic biomolecules. The concentrations of solid lipid, lipophilic and hydrophilic emulsifiers were set as the 3 independent variables. Mean particle size (Z-Ave), polydispersity index (PI) and zeta potential (ZP) were set as the dependent variables. The selected optimized parameters were set as 1.0 wt% of solid lipid, 0.25 wt% of lipophilic emulsifier and 1.5 wt% of hydrophilic emulsifier. The coating of SLNs with sodium alginate was found to improve the ZP of the lipid particles and these results suggest that the ideal concentration was 0.75 wt%. The influence of low pH (i.e., about 2-3) in the inner aqueous phase was stronger than higher pH values, contributing for the production of larger droplet sizes. Nevertheless, these systems can be useful for the incorporation of biomolecules requiring a pH ranging between 4 and 10. SLNs based on multiple emulsions technology were found to be a promising approach for the incorporation of several hydrophilic drugs, such as proteins and peptides.