{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:44:54Z","timestamp":1792118694018,"version":"4.4.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["CB A1-S-39237"],"award-info":[{"award-number":["CB A1-S-39237"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Depression poses a significant global health challenge, affecting an estimated 300 million people worldwide. While amitriptyline (Ami) remains one of the most effective antidepressants, its numerous side-effects contribute to a high dropout rate among patients. Addressing this issue requires exploring methods to enhance its bioavailability and reduce dosage. In this study, we describe a technique for producing amitriptyline nanoparticles (Ami-NPs) to improve the drug\u2019s efficiency. The effectiveness was assessed by comparing the dose-response curves of Ami-NPs and non-encapsulated Ami in male and female Wistar rats subjected to the forced swimming test (FST). Ami-NPs were fabricated using nanoprecipitation, with a copolymer of poly (methyl vinyl ether\/maleic acid) as the encapsulant, and a 3% solution of poloxamer F-127 as surfactant stabilizer. A Box-Behnken design was used to optimize the production of Ami-NPs, resulting in nanoparticles with the following optimal characteristics: a size of 198.6 \u00b1\u2009 38.1\u2009nm, a polydispersity index of 0.005 \u00b1\u2009 0.03\u2009nm, a zeta potential of -32 \u00b1\u2009 6 mV, and encapsulation efficiency of 79.1 \u00b1\u2009 7.4%. Ami-NPs showed higher potency and efficacy in reducing immobility during the FST (ED\n                    <jats:sub>50<\/jats:sub>\n                    =\u2009 7.06\u2009mg\/kg, E\n                    <jats:sub>max<\/jats:sub>\n                    =\u2009 41.1%), compared to amitriptyline in solution (Ami-S) (ED\n                    <jats:sub>50<\/jats:sub>\n                    =\u2009 11.89\u2009mg\/kg, E\n                    <jats:sub>max<\/jats:sub>\n                    =\u2009 33.2%). The E\n                    <jats:sub>max<\/jats:sub>\n                    of Ami-NPs occurred at 12\u2009mg\/kg, while Ami-S peaked at 15.8\u2009mg\/kg. In the open field test, only treatment with Ami-NPs (12\u2009mg\/kg) and the empty nanoparticles increased immobility. In the elevated plus-maze, treatment with Ami-NPs (12\u2009mg\/kg) significantly reduced closed-arm entries (2.1 \u00b1\u2009 0.6), compared to control solution (9.5 \u00b1\u2009 1.8), control nanoparticles (8 \u00b1\u2009 1.0) and Ami-S (11.5 \u00b1\u2009 2). In the marble burying test, Ami-NPs (12\u2009mg\/kg) significantly reduced buried marbles (2.4 \u00b1\u2009 0.4) compared to control nanoparticles (8.7 \u00b1\u2009 1.2). These findings suggest that Ami-NPs could be a promising approach to enhance Ami bioavailability, thereby increasing its potency and antidepressant efficacy, while improving anxiolytic-like effects.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0316389","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T13:22:49Z","timestamp":1740748969000},"page":"e0316389","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats"],"prefix":"10.1371","volume":"20","author":[{"given":"Ram\u00f3n Eduardo","family":"Valadez-Lemus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"G\u00f3ngora-Alfaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9508-9332","authenticated-orcid":true,"given":"Juana Mar\u00eda","family":"Jim\u00e9nez-Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9666-5490","authenticated-orcid":true,"given":"Javier","family":"Alamilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00e9stor","family":"Mendoza-Mu\u00f1oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"pone.0316389.ref001","unstructured":"WHO. 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