Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats.
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 explori...
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Public Library of Science (PLoS)
2025-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0316389 |
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| author | Ramón Eduardo Valadez-Lemus José L Góngora-Alfaro Juana María Jiménez-Vargas Javier Alamilla Néstor Mendoza-Muñoz |
| author_facet | Ramón Eduardo Valadez-Lemus José L Góngora-Alfaro Juana María Jiménez-Vargas Javier Alamilla Néstor Mendoza-Muñoz |
| author_sort | Ramón Eduardo Valadez-Lemus |
| collection | DOAJ |
| description | 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's 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 ± 38.1 nm, a polydispersity index of 0.005 ± 0.03 nm, a zeta potential of -32 ± 6 mV, and encapsulation efficiency of 79.1 ± 7.4%. Ami-NPs showed higher potency and efficacy in reducing immobility during the FST (ED50 = 7.06 mg/kg, Emax = 41.1%), compared to amitriptyline in solution (Ami-S) (ED50 = 11.89 mg/kg, Emax = 33.2%). The Emax of Ami-NPs occurred at 12 mg/kg, while Ami-S peaked at 15.8 mg/kg. In the open field test, only treatment with Ami-NPs (12 mg/kg) and the empty nanoparticles increased immobility. In the elevated plus-maze, treatment with Ami-NPs (12 mg/kg) significantly reduced closed-arm entries (2.1 ± 0.6), compared to control solution (9.5 ± 1.8), control nanoparticles (8 ± 1.0) and Ami-S (11.5 ± 2). In the marble burying test, Ami-NPs (12 mg/kg) significantly reduced buried marbles (2.4 ± 0.4) compared to control nanoparticles (8.7 ± 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. |
| format | Article |
| id | doaj-art-ce511c16274646c89e5be9ea7ea77f42 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-ce511c16274646c89e5be9ea7ea77f422025-08-20T01:50:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031638910.1371/journal.pone.0316389Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats.Ramón Eduardo Valadez-LemusJosé L Góngora-AlfaroJuana María Jiménez-VargasJavier AlamillaNéstor Mendoza-MuñozDepression 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's 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 ± 38.1 nm, a polydispersity index of 0.005 ± 0.03 nm, a zeta potential of -32 ± 6 mV, and encapsulation efficiency of 79.1 ± 7.4%. Ami-NPs showed higher potency and efficacy in reducing immobility during the FST (ED50 = 7.06 mg/kg, Emax = 41.1%), compared to amitriptyline in solution (Ami-S) (ED50 = 11.89 mg/kg, Emax = 33.2%). The Emax of Ami-NPs occurred at 12 mg/kg, while Ami-S peaked at 15.8 mg/kg. In the open field test, only treatment with Ami-NPs (12 mg/kg) and the empty nanoparticles increased immobility. In the elevated plus-maze, treatment with Ami-NPs (12 mg/kg) significantly reduced closed-arm entries (2.1 ± 0.6), compared to control solution (9.5 ± 1.8), control nanoparticles (8 ± 1.0) and Ami-S (11.5 ± 2). In the marble burying test, Ami-NPs (12 mg/kg) significantly reduced buried marbles (2.4 ± 0.4) compared to control nanoparticles (8.7 ± 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.https://doi.org/10.1371/journal.pone.0316389 |
| spellingShingle | Ramón Eduardo Valadez-Lemus José L Góngora-Alfaro Juana María Jiménez-Vargas Javier Alamilla Néstor Mendoza-Muñoz Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. PLoS ONE |
| title | Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. |
| title_full | Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. |
| title_fullStr | Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. |
| title_full_unstemmed | Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. |
| title_short | Nanoencapsulation of amitriptyline enhances the potency of antidepressant-like effects and exhibits anxiolytic-like effects in Wistar rats. |
| title_sort | nanoencapsulation of amitriptyline enhances the potency of antidepressant like effects and exhibits anxiolytic like effects in wistar rats |
| url | https://doi.org/10.1371/journal.pone.0316389 |
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