Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba Keratitis inducing cell death and autophagy in Acanthamoeba polyphaga

[Display omitted] Statins are effective sterol lowering agents with high amoebicidal activity. Nevertheless, due to their poor aqueous solubility, they remain underused especially in eye drop formulation. The aim of the present study is to develop Pitavastatin loaded nanoparticles suitable for ophth...

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Published in:European journal of pharmaceutics and biopharmaceutics 2022-11, Vol.180, p.11-22
Main Authors: Sifaoui, Ines, Díaz-Rodríguez, Patricia, Rodríguez-Expósito, Rubén L, Reyes-Batlle, María, López-Arencibia, Atteneri, Salazar Villatoro, Lizbeth, Castelan-Ramírez, Ismael, Omaña-Molina, Maritza, Oliva, Alexis, Piñero, José E., Lorenzo-Morales, Jacob
Format: Article
Language:English
Subjects:
Acanthamoeba spp
Pitavastatin
Polymeric Nanoparticles
Programmed cell death
Tubulin
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Summary:[Display omitted] Statins are effective sterol lowering agents with high amoebicidal activity. Nevertheless, due to their poor aqueous solubility, they remain underused especially in eye drop formulation. The aim of the present study is to develop Pitavastatin loaded nanoparticles suitable for ophthalmic administration and designed for the management of Acanthamoeba Keratitis. These nanocarriers are aimed to solve both the ophthalmic route-associated problems and the limited aqueous drug solubility issues of Pitavastatin. Nanoparticles were obtained by a nanoprecipitation-solvent displacement method and their amoebicidal activity was evaluated against four strains of Acanthamoeba: A. castellanii Neff, A. polyphaga, A. griffini and A. quina. In Acanthamoeba polyphaga, the effect of the present nanoparticles was investigated with respect to the microtubule distribution and several programmed cell death features. Nanoparticles were able to eliminate all the tested strains and Acanthamoeba polyphaga was determined to be the most resistance strain. Nanoparticles induced chromatin condensation, autophagic vacuoles and mitochondria dysfunction.
ISSN:0939-6411
1873-3441
DOI:10.1016/j.ejpb.2022.09.020