SOLID LIPID NANOPARTICLES AS A STRATEGY TO IMPROVE THE IN VITRO ANTIMICROBIAL ACTIVITY OF ITRACONAZOLE.

In the last decades, increasing attention has been paid to the development of solid lipid nanoparticles (SLN) using lipids solid at room temperature such as Cetyl palmitate, Dynasan 144, Softisan S100 [1,2] and exploiting different methods for their preparation, among which high pressure homogenization, oil-in-water microemulsion method, solvent displacement, solvent emulsification-evaporation technique [3]. Here we aimed to prepare a new formulation of lipid nanoparticles using an FDA approved lipid, characterized by a low fusion temperature, and exploiting an eco-friendly procedure for the nanoparticles reparation. In particular, a variation of the PIT method was developed in order to obtain a suspension to be easily purified by a simple procedure. The SLN were characterized by technological and in vitro biological studies to evaluate: mean particle size, polidispersity, ζ-potential, thermoanalysis (DSC) and antimicrobial activity. In order to select the ideal formulation, SLN were prepared with different amount of lipid matrix. PCS measurements allow to select the systems prepared with 10% w/w of solid lipid, due to its small particle size (<200 nm) homogeneously dispersed (PDI<0.3). After ultracentrifugation all systems maintained their properties in terms of mean particle size and homogeneity, thus confirming that ultracentrifugation can be used as a proper method for the SLN purification from the excess of surfactants. Highly positive ζ-potential values were found due to the addition of a proper amount of the cationic lipid DDAB. All systems showed a good stability when stored at 25°C, as confirmed by Turbiscan transmission profiles. The incorporation of itraconazole did not significantly modify the physico-chemical properties of the lipid nanosuspensions. Furthermore, DSC thermograms confirmed the incorporation of the lipid compound in the inner core of the SLN, that allowed a prolonged and sustained drug release. The antimicrobial activity of two different formulations was determined in vitro on C. albicans wild strains, using a broth microdilution method according to CLSI M27-A2. Itraconazole loaded-SLN showed lower MIC values than the free drug, in the range of one up to two-fold dilutions. Therefore, the SLN presented in this work are a promising system for the local delivery of itraconazole, for the treatment of infections due to C. albicans.