Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes
Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, chole...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2846 |
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| author | Elmira A. Vasilieva Darya A. Kuznetsova Farida G. Valeeva Denis M. Kuznetsov Andrey V. Zakharov Syumbelya K. Amerhanova Alexandra D. Voloshina Irina V. Zueva Konstantin A. Petrov Lucia Ya. Zakharova |
| author_facet | Elmira A. Vasilieva Darya A. Kuznetsova Farida G. Valeeva Denis M. Kuznetsov Andrey V. Zakharov Syumbelya K. Amerhanova Alexandra D. Voloshina Irina V. Zueva Konstantin A. Petrov Lucia Ya. Zakharova |
| author_sort | Elmira A. Vasilieva |
| collection | DOAJ |
| description | Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%. |
| first_indexed | 2024-03-09T15:57:11Z |
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| id | doaj.art-2e56ae732e4c47d3ab25d3ee9aaa2469 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:57:11Z |
| publishDate | 2022-12-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2e56ae732e4c47d3ab25d3ee9aaa24692023-11-24T17:23:02ZengMDPI AGPharmaceutics1999-49232022-12-011412284610.3390/pharmaceutics14122846Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded ChitosomesElmira A. Vasilieva0Darya A. Kuznetsova1Farida G. Valeeva2Denis M. Kuznetsov3Andrey V. Zakharov4Syumbelya K. Amerhanova5Alexandra D. Voloshina6Irina V. Zueva7Konstantin A. Petrov8Lucia Ya. Zakharova9Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088 Kazan, RussiaChitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.https://www.mdpi.com/1999-4923/14/12/2846chitosomesarginine chitosanacetylcholinesterase reactivationintranasal deliverypralidoxime chlorideorganophosphorus compounds |
| spellingShingle | Elmira A. Vasilieva Darya A. Kuznetsova Farida G. Valeeva Denis M. Kuznetsov Andrey V. Zakharov Syumbelya K. Amerhanova Alexandra D. Voloshina Irina V. Zueva Konstantin A. Petrov Lucia Ya. Zakharova Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes Pharmaceutics chitosomes arginine chitosan acetylcholinesterase reactivation intranasal delivery pralidoxime chloride organophosphorus compounds |
| title | Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes |
| title_full | Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes |
| title_fullStr | Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes |
| title_full_unstemmed | Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes |
| title_short | Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes |
| title_sort | therapy of organophosphate poisoning via intranasal administration of 2 pam loaded chitosomes |
| topic | chitosomes arginine chitosan acetylcholinesterase reactivation intranasal delivery pralidoxime chloride organophosphorus compounds |
| url | https://www.mdpi.com/1999-4923/14/12/2846 |
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