Topical ophthalmic delivery of active ingredients can be achieved using cationic nanoemulsions. In the last decade, Novagali Pharma has successfully developed and marketed Novasorb, an advanced pharmaceutical technology for the treatment of ophthalmic diseases. This paper describes the main steps in the development of cationic nanoemulsions from formulation to evaluation in clinical trials. A major challenge of the formulation work was the selection of a cationic agent with an acceptable safety profile that would ensure a sufficient ocular surface retention time. Then, toxicity and pharmacokinetic studies were performed showing that the cationic emulsions were safe and well tolerated. Even in the absence of an active ingredient, cationic emulsions were observed in preclinical studies to have an inherent benefit on the ocular surface. Moreover, clinical trials demonstrated the efficacy and safety of cationic emulsions loaded with cyclosporine A in patients with dry eye disease. Ongoing studies evaluating latanoprost emulsion in patients with ocular surface disease and glaucoma suggest that the beneficial effects on reducing ocular surface damage may also extend to this patient population. The culmination of these efforts has been the marketing of Cationorm, a preservative-free cationic emulsion indicated for the symptomatic treatment of dry eye.

ObjectivesTopical ocular administration is the most convenient route of administration of drugs for the treatment of eye diseases. However, the bioavailability of drugs following eye instillations of eye drops is very low. Over the past 20 years, extensive efforts have been put into research to improve drug bioavailability without compromising treatment compliance and patients' quality of life.Key findingsOne of the most efficient ways to improve drug bioavailability is to increase the precorneal residence time of the eye drop formulations. As a result, new eye drops, with bioadhesive properties, have been developed based on the cationic oil-in-water (o/w) nanoemulsion technology. These low viscosity eye drop nanoemulsions have improved precorneal residence time through the electrostatic interactions between the positively charged oil nanodroplets and the negatively charged ocular surface epithelium.SummaryThis review is the first to present the benefits of this new strategy used to improve ocular drug bioavailability. The roles of the cationic agent in the stabilization of a safe cationic o/w nanoemulsion have been discussed, as well as the unexpected benefits of the cationic o/w nanoemulsion for the protection and restoration of a healthy tear film and corneal epithelium.

Cationorm® (CN) cationic nanoemulsion was demonstrated to enhance tear film (TF) stability in vivo possibly via effects on tear film lipid layer (TFLL). Therefore the interactions of CN with human meibum (MGS) and TFLL in vitro and in vivo deserve special study. MGS and CN were spread at the air/water interface of a Langmuir surface balance to ensure a range of MGS/CN oil phase ratios: 20/1, 10/1, 5/1, 3/1, 2/1 and 1/1. The films capability to reorganize during dynamic area changes was evaluated via the surface pressure-area compression isotherms and step/relaxation dilatational rheology studies. Films structure was monitored with Brewster angle microscopy. CN/TFLL interactions at the ocular surface were monitored with non-contact specular microscopy. The in vitro studies of MGS/CN layers showed that (i) CN inclusion (at fixed MGS content) increased film elasticity and thickness and that (ii) CN can compensate for moderate meibum deficiency in MGS/CN films. In vivo CN mixed with TFLL in a manner similar to CN/MGS interactions in vitro, and resulted in enhanced thickness of TFLL. In vitro and in vivo data complement each other and facilitated the study of the composition-structure-function relationship that determines the impact of cationic nanoemulsions on TF.

These data demonstrate that the CsA cationic emulsions were more effective than Restasis at delivering CsA to target tissues, thus confirming the potential advantage of cationic emulsions over anionic emulsions as vehicle for ocular drug delivery for the treatment of ocular surface diseases.

Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.