Latanoprost loaded Phytantriol Cubosomes for Glaucoma Treatment

BESSONE CAROLINA; AKHLAGHI, S. P.; DANIELA A QUINTEROS; LOH W.

Campinas y Sao Pablo

Congreso; São Paulo Advanced School on Colloids (SPSAS); 2018

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. 12 IOP is the main risk factor and the only onethat can be modified and treated. 3 . 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. Cubosomesare 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 aqueoushumor. 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 clinicalefficacy. The average particle size and zeta potential of the samples were measured usingdynamic light scattering (DLS). The cubosomes was characterized using small-angle X-rayscattering (SAXS). Isothermal titration calorimetry (ITC) was used to elucidate the interactionsbetween 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 ITCassays 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.