Latanoprost loaded Phytantriol Cubosomes for Glaucoma Treatment

BESSONE CAROLINA; AKHLAGHI PARINAZ; QUINTEROS DANIELA; LOH WATSON; ALLEMANDI DANIEL

Campinas

Simposio; São Paulo Advanced School on Colloids; 2018

Universidad Estadual de Campinas, Instituto de Quimica

Glaucoma is a degenerative optic neuropathy, which presents itself as a chronic and irreversible disease. It is characterized by increased intraocular pressure (IOP) that results in irreversible damages in all ocular nervous structures with a characteristic decrease of visual field concluding atrophic of optic nerves and posterior blindness. IOP is the main risk factor and the only one that can be modified and treated. . Liquid crystal systems, such as cubosomes, emerge as a new way of transporting drugs from their unique properties, such as biodegradables, bioadhesives and besides show a prolonged release, which makes these systems as potentially useful for administration ocular. Cubosomes are individual nanoparticles formed by the dispersion of the bicontinuous cubic phase in water.In this study, the principal goal is obtaining nanometric sized cubosomes through Top-down (TD) method and encapsulating Latanoprost for the treatment of glaucoma. Latanoprost is an esterified prodrug that has a lipophilic nature, it reduces IOP through drainage of the aqueous humor. Top-down (TD) approach was employed to prepare submicron sized liquid crystalline dispersions (cubosomes) of phytantriol in water with a solution of Pluronic®F127 (F127) as a stabilizer. In this method, the bulk liquid gel was dispersed using ultrasonication. Cubosomes were prepared at different concentrations of latanoprost close to the concentration of clinical efficacy. The average particle size and zeta potential of the samples were measured using dynamic light scattering (DLS). The cubosomes was characterized using small-angle X-ray scattering (SAXS). Isothermal titration calorimetry (ITC) was used to elucidate the interactions between the blank cubosomes and latanoprost. The loading capacity was determined, monitoring the concentration of the drug in solution by means of spectroscopic techniques such as High Performance Liquid Chromatography (HPLC). Moreover, the in vitro release of latanoprost from the cubosomes was studied using a dialysis method in cells coupled with liquid chromatography?mass spectrometry (LC/MS) technique.The cubosomes had an average particle size of approximately 200 nm with negative zeta potential values and it showed a good encapsulation efficiency of latanoprost of approximately 90%The SAXS studies revealed a double diamond Pn3m cubic structure for both blank and latanoprost-loaded cubosomes with an constant in the lattice parameter from 6 nm. The ITC assays revealing an slight exothermic process of interaction between cubosomes and the drug. Finally, in vitro release assay exhibited a sustained release in the time at each concentration evaluated.