Effect of novel stabilizers—cationic polymers on the particle size and physical stability of poorly soluble drug nanocrystals

In this study, a novel class of stabilizer, cationic polymer, was introduced into the system of nanocrystals. Taking itraconazole as a poorly soluble model drug, the influence of three cationic polymers—chitosan, N-trimethyl chitosan, and polyethyleneimine—on the properties of the nanocrystals prepared by high-pressure homogenization method was investigated. Physicochemical properties of the nanoparticles were characterized. It was demonstrated that the cationic polymers could act as both an electrostatic and steric stabilizer to facilitate particle size reduction. Factors influencing charge density and stretching state of the cationic polymers influenced the magnitude of the particle. The electrostatic stabilization effect is more prominent than that of the steric stabilizing mechanism. Drug crystalline state was not changed by the addition of cationic polymers. Physical stability of the nanocrystals with cationic polymers was remarkably improved. The in vivo antifungal efficacy of the nanocrystals was dependent on physicochemical properties and pH.From the Clinical EditorCationic polymer stabilizers were used to modify the surface of nanocrystals and the resulting stabilizing mechanisms were compared. The electrostatic stabilization effect was found to be stronger than the steric one. Crystallinity of itraconazole was unchanged by the addition of cationic polymers, while drug physical stability remarkably improved.

Graphical AbstractThe particle size and zeta potential values of the itraconazole nanoparticles stabilized by 0.5% (w/w) Lutrol F68 with CS 50, TMC 50, or PEI 25 of different concentrations at pH 5.Figure optionsDownload high-quality image (219 K)Download as PowerPoint slide