Development of Fenofibrate/Randomly Methylated β-Cyclodextrin-Loaded Eudragit® RL 100 Nanoparticles for Ocular Delivery

Abstract

Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-β-CD (RMβCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD complex. FE-loaded Eudragit® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen’s egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.

Evaluation on the inclusion behavior of β-cyclodextrins with lycorine and its hydrochloride

“…The possible interactions and inclusion modes of all inclusion complexes were investigated by 1D and 2D 1 H NMR [58] . To begin with, the chemical shifts of all inclusion complexes, β-CDs, Lyc and Lyc∙HCl were observed by 1D 1 H NMR.…”

Eudragit Films as Carriers of Lipoic Acid for Transcorneal Permeability

“…Eudragit polymers as a carrier system for ophthalmic drug release have been studied for more than a decade. The application of these polymers in ophthalmic drug delivery begins with Eudragit RL100/RS100 in suspension nanoparticle systems, having great potential because they do not present toxicity and, for their high mucoadhesion and controlled drug release [ 8 , 9 , 10 , 11 ].…”

“…An example of the aforementioned is the development of polymeric nanoparticles composed of Eudragit RL 100 and/or Eudragit RS 100 loaded with ibuprofen, amikacin or gatifloxacin/prednisolone as drug carriers to improve drug penetration and bioavailability in the anterior segment of the eye [ 12 ]. Another example is the development of dispersions and suspensions of nanoparticles of Eudragit RL100 loaded with fenofibrate for the treatment of diabetic retinopathy and macular degradation, with excellent mucoadhesive properties and sustained drug release [ 11 ].…”

Mucoadhesive Cationic Bromelain Laden Nanocarriers Restore Patency of Airway Hyperresponsive Remodeling via Nasal Route

“…[18,19] Among polymers, Eudragid RL 100, a cationic biodegradable, biocompatible, non-immunogenic and non-toxic copolymer of poly(ethylacrylate, methyl-methacrylate, and chlorotrimethyl-ammonioethyl methacrylate) is of choice for development of mucoadhesive nanoengineered biopharmaceutical therapies. [20][21][22] It exhibits mucoadhesive behavior by selectively interacting with negatively charged mucosal surface and improves residence time of drug at absorption site. [23] Recently, Eudragit RL 100 has been successfully investigated for delivery of biopharmaceuticals.…”