Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Abstract

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.

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

“…In the tear film, the mucus barrier is comprised of membrane-associated mucins, which form a dense layer near the corneal epithelium, and secreted mucins, which form an outer layer and are less densely arrayed ( Figure 1(a) ). 1 Secreted mucins, the first line of defense in the mucus barrier, move within the tear film and bind to foreign particles, including allergens and pathogens. 1 The secreted mucins, with associated particles, and tear film are moved out to the nasolacrimal duct during blinking to rapidly clear the ocular surface.…”

“…Traditional eye drops (solutions and suspensions) are cleared from the ocular surface within 1 minute, so that ⩽5% of the drug reaches anterior eye tissues ( Figure 1(b) ). 1 , 3 , 4 In an effort to slow the clearance of drugs from the ocular surface and enhance delivery to the epithelia, mucoadhesive eye drop formulations have been developed, including polymer-based solutions, viscous gels, and mucoadhesive micro- and nanoparticles. 1 Formulations that encourage drug particles to adhere to mucins may increase the residence time of drug at the mucosal layer.…”

“… 1 , 3 , 4 In an effort to slow the clearance of drugs from the ocular surface and enhance delivery to the epithelia, mucoadhesive eye drop formulations have been developed, including polymer-based solutions, viscous gels, and mucoadhesive micro- and nanoparticles. 1 Formulations that encourage drug particles to adhere to mucins may increase the residence time of drug at the mucosal layer. However, because such formulations are likely to be largely trapped by secreted mucins and cleared from the ocular surface within minutes, these formulations do not solve the problem of delivering drugs through the mucus barrier to the cornea.…”

“…However, because such formulations are likely to be largely trapped by secreted mucins and cleared from the ocular surface within minutes, these formulations do not solve the problem of delivering drugs through the mucus barrier to the cornea. 1 , 3 …”

“…The tear film, and in particular the mucus barrier, efficiently clears topical agents from the surface of the eye before they can reach the underlying corneal and conjunctival tissues. 1 – 3 A new technology based on mucus-penetrating particles (MPPs) 1 has the potential to penetrate the mucus barrier and deliver therapeutic agents more efficiently to the ocular surface tissue. KPI-121 0.25%, an ophthalmic suspension of the ocular corticosteroid loteprednol etabonate using the MPP technology, has been approved for the short-term treatment of signs and symptoms of DED.…”