Nanosuspension: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to amphotericin B

Present limitations in the management of ophthalmic fungal infections include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure. In the present study, the potential of Eudragit RS 100 nanoparticles (NPs) as a new vehicle for the improvement of the delivery of drugs to the ocular mucosa was investigated. Amphotericin B (AmB) was chosen as a model compound because of its potential usefulness for the treatment of fungal diseases. A solvent displacement technique was used to produce AmB-loaded Eudragit NPs. These NPs had a mean size range of 150–290 nm and a zeta potential of +19–28 mV. Even after 6 months of stability study, results were unchanged, indicating the good potential for ocular application. In vitro release studies revealed that a maximum amount of drug was released within 24 hours (60%). The results obtained from microbial assay showed that the antifungal activity of drug-loaded NPs was equal to or slightly lower than that of free-AmB solution. In vivo experiments showed that, following topical instillation of nanosuspension to a rabbit's eye there was no irritation. From these results we can conclude that Eudragit RS 100 nanosuspension may represent an efficacious vehicle to deliver the drug into the eye.From the Clinical EditorAmphotericin B encapsulated into Eudragit, a mildly cationic nanoparticle, was shown to have 6 month stability, release 60% of its drug payload in dissolution within 24 hours, and elicited no irritation when instilled into rabbit eyes. The concept is being considered for local ophthalmologic therapy of fungal disease.

Graphical AbstractTEM image of nanoparticles.The NPs were successfully prepared by solvent displacement or nanoprecipitation method. The nonbiodegradable positively charged polymer Eudragit RS 100 was used, with varying ratios. The formulations were evaluated in terms of particle size, zeta potential, and differential scanning calorimetry measurements. Drug entrapment and release properties were also examined.Figure optionsDownload high-quality image (109 K)Download as PowerPoint slide