Synergistic effect of acetazolamide-(2-hydroxy)propyl β-cyclodextrin in timolol liposomes for decreasing and prolonging intraocular pressure levels

ARROYO-GARCÍA, CARMEN M.; QUINTEROS, DANIELA; PALMA, SANTIAGO D.; JIMÉNEZ DE LOS SANTOS, CESÁREO J.; MOYANO, JOSÉ R.; RABASCO, ANTONIO M.; GONZÁLEZ-RODRÍGUEZ, MARÍA LUISA

Pharmaceutics

MDPI

Año: 2021 vol. 13

he purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion com-plexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the wat