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

Abstract

Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration.

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

“…Fernandes et al studied used soybean oil as a vegetable oil that operated as an internal phase of NEs as lipid for ocular delivery [83,103]. The interfacial tension (oil and water) for soybean is 22.1 mN/m [104], its viscosity is 0.0405 Pa•s −1 at 30 • C and 0.0232 at 50 • C Pa•s −1 [105], and the density is 0.9082 and 0.9023 g/mL at 37 • C and 50 • C, respectively [106].…”

“…For example, in age-related macular degeneration, an ocular disease that affects millions of people in the world, triamcinolone acetonide has been described as an efficient drug to prevent the evolution of this disease [109]. To entrap triamcinolone acetonide in NEs with soybean oil, as an example, it is necessary to study the solubility of the drug in this lipid [83,103]. The solubility of triamcinolone acetonide is described as 95 ± 8 µg/mL in soybean oil and 4700 ± 300 µg/mL in Tween 80 (normally used as a non-ionic surfactant in formulations of ocular delivery) [110].…”

“…Poloxamer 188 (a non-ionic surfactant) has been used as a co-surfactant in NEs [83,103]. Poloxamer 188 (C 8 H 18 O 3 ) has been described elsewhere to create smaller particle size and narrower size distribution in emulsification [124].…”

Lipid Nanocarriers for Hyperproliferative Skin Diseases

“…In 1965, Gregoriadis proposed for the first time the use of phospholipids in form of liposomes for drug delivery [ 8 ]. Amphiphilic molecules, as phospholipids, have a polar region (ionic) and an apolar region [ 9 , 10 ]. When present at a concentration higher than their Critical Micellar Concentration (CMC) and excess of water, can form different types of supramolecular aggregates, such as micelles, monolayers, multilayers and liposomes [ 9 , 11 ].…”

“…These vesicles are organized in the presence of water, and, in part, the bilayer orientation is determined by the nature of the polar groups and carbon chains. Various amphiphilic compounds, containing two carbon chains, including the natural phospholipids and synthetic compounds [ 9 , 10 ], can be used as structural elements of liposomes while the production method can be fine-tuned to control the size and morphology of the vesicles [ 11 ].…”