Further investigation of nanostructured lipid carriers as an ocular delivery system: In vivo transcorneal mechanism and in vitro release study

摘要

This study was designed to provide further understanding of transcorneal mechanism of nanostructured lipid carriers (NLC). NLC labeled with fluorescent marker rhodamine B or coumarin-6 were produced by a melt emulsification method. By confocal laser scanning microscopy (CLSM), the interaction of NLC with corneal epithelia was traced and evaluated in rabbits in vivo. Thermal stability of the markers and the amorphous state were detected using thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC). The labeled NLC were characterized to be solid spherical in shape with an average diameter of 70 nm and zeta potential of -8 mV by transmission electron microscopy and dynamic light scattering, respectively. CLSM results demonstrated NLC were not directly internalized by corneal epithelia, whereas the markers themselves transferred from NLC to corneal epithelia with subsequent staining of intracellular lipophilic compartments. Furthermore, the in vitro release study using liposome dispersions as mimic biomembranes demonstrated an efficient transfer of fluorescence marker into the liposomes. This implied the deceptive particle uptake was due to a collision-induced process, during which the rapid transfer of fluorescence marker occurred by forming a complex between the nanoparticles and the biomembranes. Thus, these evidences provide further insights into NLC as an ocular delivery system.