NM133 -  for the Treatment of Dry Eye Syndrome

Nanomerics MET allows associated drugs to be efficiently carried across a number of epithelia, including the conjunctiva and cornea. Nanomerics is developing NM133, a nano-enabled form of cyclosporine A for the treatment of dry eye syndrome.  NM133 is an aqueous MET formulation able to deliver up to 8 times the amount of drug into the ocular tissues on topical application when compared to current licensed products.  This not only makes NM133 more potent at the same drug dose, but also allows a significant reduction of the amount of drug used, thus minimising the risk of off-target side effects and local irritation. In addition to an improved safety profile, NM133 offers considerable improvement in terms of convenience, as the formulation is not opaque and may be dosed once daily.

Dry eye disease (keratoconjunctivitis sicca) is a multifactorial condition characterised by tear hyperosmolarity, tear film instability and ocular surface inflammation [1].  The disease is prevalent in older people and affects an estimated 20% of the female population over the age of 60 in the UK and an estimated 15% of the US population over the age of 65 [2-4].  The disease is more prevalent in older females [2,3].  Symptoms include visual impairment and patient discomfort described as stinging, burning, a foreign body sensation and eye pain, which in severe cases is disabling [4].  The condition is driven by tear film hyperosmolarity (either due to evaporative loss or low aqueous secretion) which then leads to the release of inflammatory cytokines; these inflammatory mediators cause a reduction in mucus producing goblet cells, reduced mucus production and ultimately damage to the epithelial surface; the resulting tear film instability sets up a vicious cycle of pathology [1, 5]

Cyclosporine A is an immunosuppressant that works by inhibiting the interleukin 2 activation of lymphocytes and thus it reduces the attack on the exocrine epithelia of the lachrymal glands; this results in increased tear secretion and increased tear film stability [5]. Cyclosporine A also decreases apoptosis and thus increases the density mucus producing goblet cells, leading to a restoration of the damaged ocular epithelium [5].  In Dry Eye patients, cyclosporine A is effective and it works by increasing ocular surface goblet cell density and tear fluid volume from the accessory lachrymal glands [6].  A meta analysis of 1660 participants in 12 trials revealed that topical cyclosporine A is effective in improving the symptoms of Dry Eye Syndrome patients [6].

Cyclosporine A is an extremely hydrophobic drug and therefore commercial formulations are based on oil-in-water emulsions. NM133 offers a completely new approach to the delivery of such compounds. Using the patent protected Molecular Envelope Technology (MET) NM133 effectively wraps and solubilises cyclosporine A in a protective cover, helping it across the epithelial barriers of the eye. The technology is applicable to other compounds and additional products are in development for undisclosed indications.


[1]  Lemp MA, Foulkes GN. The definition and classification of dry eye disease. Dry Eye Workshop 2007.

[2]  Kymionis GD, Bouzoukis DI, Diakonis VF, Siganos C. Treatment of chronic dry eye: focus on cyclosporine. Clinical ophthalmology. 2008; 2(4): 829-36.

[3]  Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clinical ophthalmology. 2009; 3: 405-12.

[4]  Vehof J, Kozareva D, Hysi PG, Hammond CJ. Prevalence and risk factors of dry eye disease in a British female cohort. Br J Ophthalmol. 2014.

[5]  Mantelli F, Massaro-Giordano M, Macchi I, Lambiase A, Bonini S. The cellular mechanisms of dry eye: from pathogenesis to treatment. J Cell Physiol. 2013; 228(12): 2253-6.

[6] Zhou XQ, Wei RL. Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis. Cornea. 2014; 33(7): 760-7.