PEGylation and surface functionalization of liposomes containing drug nanocrystals for cell-targeted delivery

Abstract Liposomal formulations have important therapeutic applications in anti-cancer treatments but current formulations suffer from serious side effects, high dosage requirements, and prolonged treatment. In this study, PEGylated azide-functionalized liposomes containing drug nanocrystals were investigated with the aim of increasing the drug payload and achieving functionalization for targeted delivery. Liposomes were characterized using cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small and ultra-small angle neutron scattering (SANS/USANS) and small and wide angle X-ray scattering (SAXS/WAXS). Cryo-TEM showed the dimensions of nanocrystal-loaded liposomes and the change of shape from spherical to elongated after the formation of nanocrystals, and SANS/USANS results confirmed the asymmetric particle shape. SAXS/WAXS confirmed that the crystalline drug only occurred in freeze-thawed samples and correlated with a newly unidentified polymorphic form of ciprofloxacin. Using a small molecule dye, dibenzocyclooctyne (DBCO)-cy5, specific conjugation between DBCO groups and surface azide groups on the liposomes was confirmed; this indicates the promise of this system for tumour-targeted delivery.