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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Veröffentlicht in: | European journal of pharmaceutics and biopharmaceutics 2022-11, Vol.180, p.11-22 |
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creator | 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 |
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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. |
doi_str_mv | 10.1016/j.ejpb.2022.09.020 |
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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.</description><identifier>ISSN: 0939-6411</identifier><identifier>EISSN: 1873-3441</identifier><identifier>DOI: 10.1016/j.ejpb.2022.09.020</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Acanthamoeba spp ; Pitavastatin ; Polymeric Nanoparticles ; Programmed cell death ; Tubulin</subject><ispartof>European journal of pharmaceutics and biopharmaceutics, 2022-11, Vol.180, p.11-22</ispartof><rights>2022 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-27eaca935ed1d63879315446ae751d732a80c6690e034658ef63fda8f851a6193</citedby><cites>FETCH-LOGICAL-c377t-27eaca935ed1d63879315446ae751d732a80c6690e034658ef63fda8f851a6193</cites><orcidid>0000-0002-0181-5821 ; 0000-0002-5649-8333 ; 0000-0002-7576-2013 ; 0000-0001-5881-4638 ; 0000-0002-3858-836X ; 0000-0002-4661-4257</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejpb.2022.09.020$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids></links><search><creatorcontrib>Sifaoui, Ines</creatorcontrib><creatorcontrib>Díaz-Rodríguez, Patricia</creatorcontrib><creatorcontrib>Rodríguez-Expósito, Rubén L</creatorcontrib><creatorcontrib>Reyes-Batlle, María</creatorcontrib><creatorcontrib>López-Arencibia, Atteneri</creatorcontrib><creatorcontrib>Salazar Villatoro, Lizbeth</creatorcontrib><creatorcontrib>Castelan-Ramírez, Ismael</creatorcontrib><creatorcontrib>Omaña-Molina, Maritza</creatorcontrib><creatorcontrib>Oliva, Alexis</creatorcontrib><creatorcontrib>Piñero, José E.</creatorcontrib><creatorcontrib>Lorenzo-Morales, Jacob</creatorcontrib><title>Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba Keratitis inducing cell death and autophagy in Acanthamoeba polyphaga</title><title>European journal of pharmaceutics and biopharmaceutics</title><description>[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.</description><subject>Acanthamoeba spp</subject><subject>Pitavastatin</subject><subject>Polymeric Nanoparticles</subject><subject>Programmed cell death</subject><subject>Tubulin</subject><issn>0939-6411</issn><issn>1873-3441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhi0EEkvpH-DkI5cEO07sBHFZVXxUVIJDe7Zm7UnXq8QOtlNpfwr_to6WC5ee5jDv82pGDyEfOKs54_LTqcbTcqgb1jQ1G2rWsFdkx3slKtG2_DXZsUEMlWw5f0vepXRijLWq63fk72-X4QlShuw8nQJYtNSDDwvE7MyE6TPd07SW1GFCGpZjPsI0O0NzRMgz-kzHEOnegC-bOeAB6E-MpS67RJ23q3H-kRqcJmoLcaTgLYU1lyp4PJfE_-wSpvO2gffkzQhTwut_84o8fPt6f_Ojuvv1_fZmf1cZoVSuGoVgYBAdWm6l6NUgeNe2ElB13CrRQM-MlANDJlrZ9ThKMVrox77jIPkgrsjHS-8Sw58VU9azS9u54DGsSTeK91Io3jUl2lyiJoaUIo56iW6GeNac6c2DPunNg948aDbo4qFAXy4QlieeHEadjENv0LqIJmsb3Ev4Mz-LlHA</recordid><startdate>202211</startdate><enddate>202211</enddate><creator>Sifaoui, Ines</creator><creator>Díaz-Rodríguez, Patricia</creator><creator>Rodríguez-Expósito, Rubén L</creator><creator>Reyes-Batlle, María</creator><creator>López-Arencibia, Atteneri</creator><creator>Salazar Villatoro, Lizbeth</creator><creator>Castelan-Ramírez, Ismael</creator><creator>Omaña-Molina, Maritza</creator><creator>Oliva, Alexis</creator><creator>Piñero, José E.</creator><creator>Lorenzo-Morales, Jacob</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0181-5821</orcidid><orcidid>https://orcid.org/0000-0002-5649-8333</orcidid><orcidid>https://orcid.org/0000-0002-7576-2013</orcidid><orcidid>https://orcid.org/0000-0001-5881-4638</orcidid><orcidid>https://orcid.org/0000-0002-3858-836X</orcidid><orcidid>https://orcid.org/0000-0002-4661-4257</orcidid></search><sort><creationdate>202211</creationdate><title>Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba Keratitis inducing cell death and autophagy in Acanthamoeba polyphaga</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-27eaca935ed1d63879315446ae751d732a80c6690e034658ef63fda8f851a6193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acanthamoeba spp</topic><topic>Pitavastatin</topic><topic>Polymeric Nanoparticles</topic><topic>Programmed cell death</topic><topic>Tubulin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sifaoui, Ines</creatorcontrib><creatorcontrib>Díaz-Rodríguez, Patricia</creatorcontrib><creatorcontrib>Rodríguez-Expósito, Rubén L</creatorcontrib><creatorcontrib>Reyes-Batlle, María</creatorcontrib><creatorcontrib>López-Arencibia, Atteneri</creatorcontrib><creatorcontrib>Salazar Villatoro, Lizbeth</creatorcontrib><creatorcontrib>Castelan-Ramírez, Ismael</creatorcontrib><creatorcontrib>Omaña-Molina, Maritza</creatorcontrib><creatorcontrib>Oliva, Alexis</creatorcontrib><creatorcontrib>Piñero, José E.</creatorcontrib><creatorcontrib>Lorenzo-Morales, Jacob</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sifaoui, Ines</au><au>Díaz-Rodríguez, Patricia</au><au>Rodríguez-Expósito, Rubén L</au><au>Reyes-Batlle, María</au><au>López-Arencibia, Atteneri</au><au>Salazar Villatoro, Lizbeth</au><au>Castelan-Ramírez, Ismael</au><au>Omaña-Molina, Maritza</au><au>Oliva, Alexis</au><au>Piñero, José E.</au><au>Lorenzo-Morales, Jacob</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba Keratitis inducing cell death and autophagy in Acanthamoeba polyphaga</atitle><jtitle>European journal of pharmaceutics and biopharmaceutics</jtitle><date>2022-11</date><risdate>2022</risdate><volume>180</volume><spage>11</spage><epage>22</epage><pages>11-22</pages><issn>0939-6411</issn><eissn>1873-3441</eissn><abstract>[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.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.ejpb.2022.09.020</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-0181-5821</orcidid><orcidid>https://orcid.org/0000-0002-5649-8333</orcidid><orcidid>https://orcid.org/0000-0002-7576-2013</orcidid><orcidid>https://orcid.org/0000-0001-5881-4638</orcidid><orcidid>https://orcid.org/0000-0002-3858-836X</orcidid><orcidid>https://orcid.org/0000-0002-4661-4257</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acanthamoeba spp Pitavastatin Polymeric Nanoparticles Programmed cell death Tubulin |
title | Pitavastatin loaded nanoparticles: A suitable ophthalmic treatment for Acanthamoeba Keratitis inducing cell death and autophagy in Acanthamoeba polyphaga |
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