Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(ß-Benzyl-L-aspartate) (PEG-PBLA)

Abstract

Abstract Amphiphilic block copolymers, PEG-PBLA with different molecular weights, were synthesized and used as new stabilizers for Itraconazole nannosuspensions (ITZ-PBLA-Nanos). ITZ-PBLA-Nanos were prepared by the microprecipitation-high pressure homogenization method, and the particle size and zeta potential were measured using a ZetaSizer Nano-ZS90. Morphology and crystallinity were studied using TEM, DSC and powder X-ray. The effect of the PEG-to-PBLA ratio, and the drug-to-stabilizer ratio were investigated to obtain the optimal formulation. It was found that the optimal length of hydrophobic block was 25 BLA-NCA molecules and the optimal ratio of drug/stabilizer was 1:1, where the resulted average particle size of ITZ-PBLA-Nanos was 262.1 ± 7.13 nm with a PDI value of 0.163 ± 0.011. The images of TEM suggest that ITZ-PBLA-Nanos were rectangular in shape. ITZ existed as crystals in the nanoparticles as suggested by the DSC and XRD results. Compared with the crude drug suspensions, the dissolution rate of ITZ nanocrystals, was significantly increased and was similar to Sporanox® injection. The ITZ-PBLA-Nanos also demonstrated better dilution stability and storage stability compared with ITZ-F68-Nanos. The particle size of ITZ-PBLA-Nanos did not change significantly after incubated in rat plasma for 24 h which is a good attribute for I.V. administration. Acute toxicity tests showed that ITZ-PBLA-Nanos has the highest LD50 compared with ITZ-F68-Nanos and Sporanox® injection. ITZ-PBLA-Nanos also showed stronger inhibiting effect on the growth of Candida albicans compared with Sporanox® injection. Therefore, PEG-PBLA has a promising potential as a biocompatible stabilizer for ITZ nanosuspensions and potentially for other nanosuspensions as well.