Development of fenofibrate/cyclodextrin complex loaded eudragit nanoparticles for ocular delivery

The purpose of this study was to develop Eudragit® -nanoparticles (NPs) eye drop formulations containing fenofibrate (FE) for diabetic retinopathy and age-related macular degeneration. Due to the limited aqueous solubility of FE, it may hamper the ocular bioavailability and results in low efficiency to treat such diseases. Hence, the increased solubility of FE was determined by complexation with cyclodextrins (CDs) and CD derivatives The solubility determination was evaluated by phase-solubility technique with heating method. Among CD tested, randomly methylated-b-CD (RMbCD) exhibited the best solubilizer with the highest complexation efficiency for FE. Moreover, the water-soluble polymer i.e., Soluplus® (SOL), poloxomer 407 (P407), hydroxypropyl methyl cellulose (HPMC) or polyvinyl alcohol (PVA) was investigated for the effect of polymer on to RMbCD solubilization of FE and found that HPMC and PVA could enhance the solubility of FE/RMbCD complexes. To elucidate the inclusion FE/RMbCD complex, solid-state characterizations (FT-IR, PXRD and DSC) and solution-state characterization (1H-NMR and ROESY) techniques were performed. It indicated that there were some interactions and possibly formed FE/RMbCD inclusion complex. FE loaded Eudragit®-NPs dispersions and suspensions were developed. The physicochemical and chemical properties i.e., pH, osmolality, viscosity, particle size and size distribution and zeta potential were withing the acceptable range. For FE eye drop suspensions, they were easily resuspended and the FE solid particles sizes were below 10 µm indicated possibly no irritation to the eye. Furthermore, in-vitro mucoadhesion and in-vitro release studies revealed that PVA stabilized FE/RMbCD loaded Eudragit®-NPs suspensions had excellent mocoadehesive property and performed sustained release of FE. The hemolytic activity and in vitro cytotoxicity test were performed, and it showed that FE formulations were low hemolysis, cytocompatibility and moderate irritation to the eyes. It was concluded that the topical eye drop suspensions containing FE/RMbCD complex in Eudragit®-NPs were successfully developed and had a potential for further in-vivo testing.