Recent Patents on Ophthalmic Nanoformulations and Therapeutic Implications

Abstract

Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches. The effective treatment of ocular diseases using conventional eye drops is often hampered by factors such as: physiological barriers, rapid elimination, protein binding, and enzymatic drug degradation. Combined, these factors are known to contribute to reduced ocular residence time and poor bioavailability. Recent research studies demonstrated that NF can significantly enhance the therapeutic efficacy and bioavailability of ocular drugs, compared to the established ophthalmic drug delivery strategies. The research studies resulted in a number of patent inventions, reporting a significant increase in therapeutic efficacy for various chronic ocular disease states of both the anterior and posterior ocular segments. This article reviews these patent disclosures in detail and emphasizes the therapeutic advantages conferred by the following nanoformulation approaches: Calcium Phosphate (CaP) nanoparticles, Liposomes, Nanoemulsions, Nanomicelles, and Hydrogels. The nanoformulation approaches were shown to enhance the ocular bioavailability by reducing the drugprotein binding, increasing the corneal resident time, enhancing the drug permeability and providing a sustained drug release. Further, the article discusses United States Food and Drug Administration (USFDA) approved ocular drugs employing nanotechnology and future developments. It should be noted that, despite the potential therapeutic promise demonstrated by nanotechnology for ocular drug delivery, the bench to bed transition from patent inventions to marketed drug products has been insignificant. Majority of the discussed technologies are still in development and testing phase for commercial viability. Further, studies are in progress to assess ocular tolerance and nanotoxicity for prolonged use of NF.

Application of lipid nanoparticles to ocular drug delivery

“…can inhibit the activity of P-gp expressed on epithelial cells [60], and open corneal tight junctions by means of non-ionic surfactants present in the formulations [12]. In the treatment of posterior segment diseases, they can act as controlled release systems that reduce administration frequency.…”

“…However, in some cases this produces a sticky feel of the formulation and subsequent intolerance [60].…”

“…Compared to other vesicular systems they are chemically very stable, biodegradable, biocompatible and non-immunogenic. [12] The vesicular membrane is flexible and supports deformation stress, allowing repeated intraocular injections to treat posterior segment ocular diseases [60].…”

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“…By de inition, nano emulsions have dispersed phase in which the particle size is in the submicron or nanometer range. Nano-emulsions generally comprise of one or more amphiphilic lipid(s) or surfactants [1].To increase the bioavailability of a drug in terms of ocular disease, the time that the drug stays on the cornea must be increased. There must be a set viscosity on the ocular formulations and a way to improve the viscosity is by increasing the amount of the oil face that is present in the nano-emulsion, thereby increasing the time that the drug settles on the cornea.…”

“…Recent research studies demonstrated that nanoformulations can signi icantly enhance the therapeutic ef icacy and bioavailability of ocular drugs, compared to the established classical ophthalmic drug delivery strategies [1]. There are over seventy different conditions relating to the eye that have been characterized as an ophthalmological disease.…”