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.

Roles of biomaterials in modulating the innate immune response in ocular therapy

“…The most common immunosuppressive agents are steroids. They have been used in a large number of commercial antiinflammatory ocular drugs such as Bromfenac and INVELTYS ™ , both of which contain cross-linked PAA or chitosan polymer; they are widely used for treating post-ocular surgery inflammation, reducing post-surgery pain, and DED (Bowman et al, 2009;Schopf et al, 2015;Trattler and Hosseini, 2017;Kim et al, 2018;Gupta and Venkateswaran, 2021). Steroidal immunosuppressants have several drawbacks; they require high administration dosages, frequent injections in chronic ocular inflammatory diseases that lead to defects in the innate immune system, and other long-term side effects such as cataracts and IOP in the eye.…”

Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update

“…AR-13503 (NCT03835884) and AR-1105 (NCT03739593) were designed as intravitreal implants for treating AMD and diabetic macular edema [ 3 , 240 ]. Several other under clinical trial ophthalmic nanomedicines, include Taxol (Paclitaxel albumin-stabilized nanoparticle formulation), which has done phase II clinical trial for treating intraocular melanoma [ 241 ]; GB-102 (Sunitinib malate), in phase I clinical trial for AMD therapy [ 242 ]; KPI-121 (1% and 0.25% loteprednol etabonate), is currently in phase III clinical trial for the treatment of ocular infection, irritation and inflammation [ 243 ] and OCS-01 (dexamethasone cylcodextrin) has done phase II clinical trial for treating eye inflammation and pain [ 244 ] (Table 2 ). By enhancing the nano-based material numbers on the market or in the clinical studies, it seems that the development of nano-based technologies in ocular disease treatment is a hopeful strategy, though further studies and research are needed for the delivery of nanostructure to the eye [ 193 ].…”

Practical Guidance for the Use of Loteprednol Etabonate Ophthalmic Suspension 0.25% in the Management of Dry Eye Disease

“…When patients present with a DED flare, KP-121 0.25% therapy is an excellent adjunct. 34 Its favorable pharmacologic profile allows for delivery of loteprednol etabonate onto the ocular surface with high concentration and rapid breakdown, decreasing adverse effects such as elevated intraocular pressure or cataract formation. KP-121 0.25% should be administered four times a day for two weeks during the course of a DED flare to relieve the patient's acute symptomatology and also quell the cycle of ocular surface inflammation.…”

“…KPI-121 0.25% can be used in place of traditional topical ophthalmic corticosteroids to optimize the ocular surface before cataract surgery or refractive surgery as a stable ocular surface is critical when obtaining biometric measurements for intraocular lens power calculations or when obtaining refractions for refractive surgery treatment planning to ensure patients obtain excellent postoperative visual outcomes. 34,35 Similarly, ocular surface disease can worsen after cataract or refractive surgery, especially if it is not treated adequately pre-operatively, and KP-121 0.25% can be used for short-term treatment of DED in the pre-and post-surgical time frames.…”