The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

Abstract

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film's ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.

Keywords: KPI-121; dry eye disease; loteprednol etabonate; mucus-penetrating particles; nanoparticles; ocular mucus; ocular surface.

Figure 1.

Illustration of (a) the ocular surface and tear film before drug delivery, (b) clearing of traditional drug particles from the tear film, and (c) penetration of drug using the mucus-penetrating particle (MPP) technology.

Figure 2.

Pharmacokinetic parameters of loteprednol etabonate in New Zealand white rabbit cornea and conjunctiva. The mean ± SEM loteprednol etabonate (a) C_max and (b) AUC_0–12h for rabbits receiving a single ocular dose of loteprednol etabonate ophthalmic suspension 0.5% or loteprednol etabonate MPP suspension 0.4% is depicted. AUC_0–12h, area under the concentration–time curve from time 0 to 12 hours; C_max, maximum concentration; MPP, mucus-penetrating particle; SEM, standard error of the mean.