Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies

Ciprofloxacin is one of the most effective antibiotics, but it is characterized by a range of side effects. Elaboration of drug-releasing systems which allow to diminish toxicity of ciprofloxacin is a challenging task in medicinal chemistry. The current study is focused on development of new ciprofl...

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Main Authors: Anton R. Egorov, Aleh V. Kurliuk, Vasili V. Rubanik, Anatoly A. Kirichuk, Omar Khubiev, Roman Golubev, Nikolai N. Lobanov, Alexander G. Tskhovrebov, Andreii S. Kritchenkov
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/24/8865
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author Anton R. Egorov
Aleh V. Kurliuk
Vasili V. Rubanik
Anatoly A. Kirichuk
Omar Khubiev
Roman Golubev
Nikolai N. Lobanov
Alexander G. Tskhovrebov
Andreii S. Kritchenkov
author_facet Anton R. Egorov
Aleh V. Kurliuk
Vasili V. Rubanik
Anatoly A. Kirichuk
Omar Khubiev
Roman Golubev
Nikolai N. Lobanov
Alexander G. Tskhovrebov
Andreii S. Kritchenkov
author_sort Anton R. Egorov
collection DOAJ
description Ciprofloxacin is one of the most effective antibiotics, but it is characterized by a range of side effects. Elaboration of drug-releasing systems which allow to diminish toxicity of ciprofloxacin is a challenging task in medicinal chemistry. The current study is focused on development of new ciprofloxacin releasing systems (CRS). We found that ultrasound efficiently promotes <i>N,N′</i>-dicyclohexyl carbodiimide-mediated coupling between COOH and NH<sub>2</sub> functionalities in water. This was used for conjugation of ciprofloxacin to chitosan. The obtained ciprofloxacin/chitosan conjugates are capable of forming their self-assembled nanoparticles (SANPs) in aqueous medium. The SANPs can be additionally loaded by ciprofloxacin to form new CRS. The CRS demonstrated high loading and encapsulation efficiency and they are characterized by extended release profile (20 h). The elaborated CRS were tested in vivo in rats. The in vivo antibacterial effect of the CRS exceeded that of the starting ciprofloxacin. Moreover, the in vivo acute and subacute toxicity of the nanoparticles was almost identical to that of the chitosan, which is considered as the non-toxic biopolymer.
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spelling doaj.art-6e8dcbdb6a8c429ab302c2c95a7e96c02023-11-24T16:58:46ZengMDPI AGMolecules1420-30492022-12-012724886510.3390/molecules27248865Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) StudiesAnton R. Egorov0Aleh V. Kurliuk1Vasili V. Rubanik2Anatoly A. Kirichuk3Omar Khubiev4Roman Golubev5Nikolai N. Lobanov6Alexander G. Tskhovrebov7Andreii S. Kritchenkov8Faculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaDepartment of General and Clinical Pharmacology, Vitebsk State Medical University, Frunze Av. 27, 210009 Vitebsk, BelarusMetal Physics Laboratory, Institute of Technical Acoustics NAS of Belarus, Ludnikova Prosp. 13, 210009 Vitebsk, BelarusFaculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaFaculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaMetal Physics Laboratory, Institute of Technical Acoustics NAS of Belarus, Ludnikova Prosp. 13, 210009 Vitebsk, BelarusFaculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaFaculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaFaculty of Science, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St. 6, Moscow 117198, RussiaCiprofloxacin is one of the most effective antibiotics, but it is characterized by a range of side effects. Elaboration of drug-releasing systems which allow to diminish toxicity of ciprofloxacin is a challenging task in medicinal chemistry. The current study is focused on development of new ciprofloxacin releasing systems (CRS). We found that ultrasound efficiently promotes <i>N,N′</i>-dicyclohexyl carbodiimide-mediated coupling between COOH and NH<sub>2</sub> functionalities in water. This was used for conjugation of ciprofloxacin to chitosan. The obtained ciprofloxacin/chitosan conjugates are capable of forming their self-assembled nanoparticles (SANPs) in aqueous medium. The SANPs can be additionally loaded by ciprofloxacin to form new CRS. The CRS demonstrated high loading and encapsulation efficiency and they are characterized by extended release profile (20 h). The elaborated CRS were tested in vivo in rats. The in vivo antibacterial effect of the CRS exceeded that of the starting ciprofloxacin. Moreover, the in vivo acute and subacute toxicity of the nanoparticles was almost identical to that of the chitosan, which is considered as the non-toxic biopolymer.https://www.mdpi.com/1420-3049/27/24/8865chitosanciprofloxacinantibacterial activity
spellingShingle Anton R. Egorov
Aleh V. Kurliuk
Vasili V. Rubanik
Anatoly A. Kirichuk
Omar Khubiev
Roman Golubev
Nikolai N. Lobanov
Alexander G. Tskhovrebov
Andreii S. Kritchenkov
Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
Molecules
chitosan
ciprofloxacin
antibacterial activity
title Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
title_full Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
title_fullStr Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
title_full_unstemmed Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
title_short Chitosan-Based Ciprofloxacin Extended Release Systems: Combined Synthetic and Pharmacological (In Vitro and In Vivo) Studies
title_sort chitosan based ciprofloxacin extended release systems combined synthetic and pharmacological in vitro and in vivo studies
topic chitosan
ciprofloxacin
antibacterial activity
url https://www.mdpi.com/1420-3049/27/24/8865
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