Abstract
BACKGROUND: Amphotericin B (AmB) nanoformulations have been widely used for the treatment of invasive fungal infections in clinical practice, all of which are lyophilized solid dosage forms that improve storage stability. The colloidal stability of reconstituted lyophilized nanoparticles in an injection medium is a critical quality attribute that directly affects their safety and efficacy during clinical use. METHODS: In the present study, the colloidal stability of commercial AmB nanoformulations, including AmB cholesteryl sulfate complex (AmB-CSC) and AmB liposome (AmB-Lipo), was evaluated using the dynamic (DLS) and static multiple light scattering (SMLS) techniques. RESULTS: Compared to the DLS technique, the SMLS technique allows for a more objective and accurate evaluation of the colloidal stability of AmB nanoformulations. The results obtained using the SMLS technique demonstrated that AmB-CSC and AmB-Lipo exhibited excellent colloidal stability in both sterile water and 5% dextrose injection. The disk-like structure of the AmB-CSC nanoparticles more readily adsorbed serum proteins to form protein corona compared to the spherical structure of AmB-Lipo after incubation with serum. Additionally, AmB-CSC and AmB-Lipo can significantly reduce the in vitro cytotoxicity and in vivo nephrotoxicity of AmB, which may be attributed to the good colloidal stability and the improved pharmacokinetic profiles of AmB nanoformulations. CONCLUSION: To the best of our knowledge, this study is the first to compare the colloidal stability of commercial AmB nanoformulations. These findings will provide useful information not only to inform the clinical use of available AmB nanoformulations but also for improving the design and conduct of translational research on novel AmB nanomedicines.