In vitro evaluation of stearylamine cationic nanoemulsions for improved ocular drug delivery

Abstract

Oil-in-water nanoemulsions (NEs) represent one of the formulation approaches to improve eye-related bio-availability of lipophilic drugs. The potential of cationic NEs is pronounced due to the electrostatic interaction of positively charged droplets with negatively charged mucins present in the tear film, providing prolonged formulation residence at the ocular surface. The aim of this study was to develop a cationic ophthalmic NE with cationic lipid stearylamine (SA) as a carrier of a positive charge. The addition of a nonionic surfactant provided the dual electro-steric stabilization of NEs and enabled tuning of SA concentration to achieve an optimal balance between its interaction with mucins and biocompatibility. Physicochemical characterization, stability profile, in vitro mucoadhesion study and biocompatibility study employing 3D HCE-T cell-based model of corneal epithelium pointed out the NE with 0.05 % (m/m) SA as the leading formulation. Minimizing SA content while retaining droplet/mucin interactions is of great importance for efficacy and safety of future ophthalmic drug products.

Delivery of Hydrophobic Drugs to the Posterior Ocular Region by Gel-in-Water Nanoemulsion

“…The zeta potential influences the precorneal residence time of emulsion at the ocular surface and formulation stability during storage. 31 According to the classical electrical double layer theory, a zeta potential value >±30 mV demonstrates good stability. 32 However, because high-molecular-weight surfactants stabilize a nanoemulsion by steric hindrance, a zeta potential value of only ±20 mV or lower can provide sufficient stability.…”

Development and Characterization of Nanoemulsions for Ophthalmic Applications: Role of Cationic Surfactants

“…In the microfluidization method, the macroemulsion is passed via micro-channels (microfluidizer) underneath high pressures and forces as shearing and cavitation generate NEs. The pressure applied in this method is around 500 to 20,000 psi [63]. This method can be used in the production of multiple NEs as well as in the production of dispersed phases with organized droplets sizes.…”

Mono- and Dicationic DABCO/Quinuclidine Composed Nanomaterials for the Loading of Steroidal Drug: 32 Factorial Design and Physicochemical Characterization

“…Among NEs, cationic NEs present prominent potential due to the electrostatic interactions occurring between the positively charged eye-droplets with the negatively charged mucins expressed at ocular surface epithelia and are responsible for the tear film maintenance [3,4]. This electrostatic interaction offers prolonged NEs residence time at the ocular surface increasing the drug absorption [5]. Topical instillations of eye-drops are the common treatment for ophthalmic 2 of 22 diseases.…”

“…Other advantages of NEs include enhanced ocular retention associated with extended effect duration, sustained drug-release, reduced systemic side-effects and, as NEs are able to interact with the tear film lipid layer, they can stay for a longer time in the conjunctival sac, acting as a drug depot [14][15][16]. Additionally, the NE droplet surface can be functionalized with cationic lipids or surfactants or polymers to form positively charged droplets, enhancing residence time [5].…”

“…T blinking and the composition of the tear are responsible for the NEs breakdown after a ministration. So, after NEs breakdown, the drug molecules are released and the oily pha of the NEs mixes with the tear film lipid layer [5]. Other advantages of NEs include e hanced ocular retention associated with extended effect duration, sustained drug-relea reduced systemic side-effects and, as NEs are able to interact with the tear film lipid lay they can stay for a longer time in the conjunctival sac, acting as a drug depot [14-1 Additionally, the NE droplet surface can be functionalized with cationic lipids or surf tants or polymers to form positively charged droplets, enhancing residence time [5].…”