Iontophoretic transport of poly(lactic-co-glycolic acid) nanoparticles across in vitro rabbit cornea

Abstract

Iontophoresis is a non-invasive technique used to transport substances of interest across tissues and this has drawn interest in ophthalmic fields to enhance delivery efficiency of topically administered drugs. Thus, there have been numerous trials to deliver small molecules across cornea into the eye using iontophoresis

however, few were reported to transport the nanoparticles. The purpose of this study was, therefore, to profile an iontophoretic transport of the nanoparticles made of a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), where the various conditions of iontophoresis were applied via the cornea of in vitro rabbit eyes. Also, iontophoresis was conducted on the simulated eyelid to minimize the potential problems caused by direct contact of an electrode to the sensitive eye surface. For this, the tablet formulation of fluorescence-tagged PLGA nanoparticles was applied onto the cornea, where the factors, such as the size of nanoparticles, amplitude of electric current and time for iontophoresis application, were varied. After the iontophoretic application of the nanoparticles, the fluorescence intensity of each of the cross-section layers of the cornea was observed with confocal fluorescence microscopy to assess the distribution of PLGA nanoparticles. The results show that there are significant differences in the delivered amount of PLGA nanoparticles into cornea according to the size of PLGA nanoparticles and time of formulation applications. Importantly, the particle size was observed to be one the most crucial factors in determining the transport of PLGA nanoparticles across cornea. In this study, however, although the intensity of electric current was varied at 0 mA to 0.5 mA, 1 mA and 2 mA, there were no statistically significant differences among the delivered amounts of PLGA nanoparticles. Under the iontophoresis conditions employed in this study, it appeared that the electric field was not properly focused on the cornea and the surface charge of the nanoparticles was not very high (~ 2 mV). Therefore, transport of PLGA nanoparticles across in vitro cornea was mostly mediated by particle diffusion.