These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases.

IntroductionTopical ophthalmic formulations of corticosteroids are commonly used to treat a variety of ocular diseases and conditions that have an inflammatory component. The purpose of this study was to evaluate the effect of the mucus-penetrating particle (MPP) technology on the pharmacokinetic profile of loteprednol etabonate in the ocular tissues of rabbits.MethodsForty-eight New Zealand White rabbits were randomly assigned to two groups (n = 3 rabbits or 6 eyes per time point) and treated with either the novel loteprednol etabonate MPP suspension formulation, 0.4% (LE-MPP 0.4%), or the commercial Lotemax®-brand loteprednol etabonate ophthalmic suspension, 0.5% (Lotemax 0.5%) (Bausch & Lomb Incorporated, Inc., Rochester, NY, USA). Samples of aqueous humor, various ocular tissues, and plasma were collected from animals over a 12-h period after a single dose of the test articles. Loteprednol etabonate concentrations were assayed using liquid chromatography–tandem mass spectrometry (LC/MS/MS).ResultsLoteprednol etabonate was rapidly absorbed into ocular tissues following administration of either formulation. A higher ocular exposure was achieved using LE-MPP 0.4%, with peak concentrations of approximately threefold higher in ocular tissues and the aqueous humor than Lotemax 0.5%.ConclusionsAdministration of LE-MPP 0.4% improved loteprednol etabonate pharmacokinetic profile in ocular tissues of rabbits. The results of this study support the premise that the MPP technology can be used to enhance ocular exposure for topically applied therapeutic agents. Further studies to assess the clinical efficacy and safety of the LE-MPP formulation are warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s40123-014-0021-z) contains supplementary material, which is available to authorized users.

The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as allergens, pathogens, and debris. In playing this pivotal role, mucus can also hinder topical delivery of therapeutics to the eye. Recent studies provide evidence that drugs formulated as traditional micro-or nanoparticles are susceptible to entrapment and rapid clearance by ocular mucus. Mucus-penetrating particles (MPPs) is a nanoparticle technology that emerged over the past decade. With a muco-inert surface and a particle size smaller than the mucus mesh size, MPPs can diffuse in ex vivo mucus essentially freely. Preclinical studies have shown that, compared with particles lacking the mucus-penetrating attributes, MPPs can improve the uniformity of drug particle distribution on mucosal surfaces and enhance drug delivery to ocular tissues.

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