Vietnam Academy of Science and Technology

Project's information

Project's title	Innovative biocompatible biodegradable systems for targeted delivery of fluoroquinolones
Project’s code	QTRU01.12/20-21
Research hosting institution	Institute of Chemistry
Coordinating unit, co-chair	Russian Foundation of Bacis Rearch
Project leader’s name	Dr. Le Nhat Thuy Giang and Prof. Victor N. Khrustalev
Project duration	01/06/2020 - 30/09/2023
Project’s budget	200 million VND
Classify	Excellent
Goal and objectives of the project	- Synthesis and biological evaluation of chitosan-triazole-ciprofloxacin conjugates; - Synthesis and biological evaluation of triazole-chitin derivative and its nanoparticles.
Main results	Polymer chitosan-triazole (4) was successfully prepared by the amidation reaction of chitosan and 2-(4-bromomethyl)-1H-1,2,3-triazol-1-yl)-5-chloro-4-methylbenzoic acid (3). This reaction was carried out in the neutral medium in the presence of DCC/DMAP at room temperature for 12 h. - The click Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) between N-(3-azido-2-hydroxypropyl)chitosan (6) and propargylic ester betaine chloride (7) afforded chitosan-triazole-betaine derivative (8). The reaction was carried out in THF at room temperature using CuI as a catalyst and DIPEA as a base. - The chitosan-triazole-ciprofloxacin conjugates 10-11 were successfully synthesized by the DCC/DMAP-mediated coupling between triazole-chitosan (4) or triazole-betaine-chitosan (8) with ciprofloxacin (9) in water. - The antibacterial effect of chitosan-triazole derivatives 4, 8 and chitosan-triazole-ciprofloxacin conjugates 10-11 against S. aureus and E. coli higher than those of chitosan. In particular, the antibacterial effect of conjugates 10-11 is comparable with those of the reference antibiotic ciprofloxacin. - The nanoparticles based on chitosan-triazole-ciprofloxacin conjugates NP10 and NP11 were prepared using the ionic gelation method. - The chitosan-triazole-ciprofloxacin conjugates 10-11 did not release ciprofloxacin during at least 80 h. The nanoparticles NP-10 released ciprofloxacin 30-35% within 50 h, meanwhile nanoparticles NP-11 released ciprofloxacin 100% in 25 h. These results revealed that the chitosan-triazole-ciprofloxacin conjugates are capable for targeted delivery of fluoroquinolones. - The click CuAAC reaction of azido-chitin and propargyl ester N,N,N-trimethylglycine chloride afforded water-soluble triazole-chitin derivative 14. - The nanoparticles based on triazole-chitin derivative 14 were prepared using the ionic gelation method. - The triazole-chitin derivative and its nanoparticles are characterized by a high in vitro antibacterial activity, which is the same or even higher than that of commercial antibiotic ampicillin and gentamicin. - The triazole-chitin derivative and its nanoparticles are non-toxic against NIH 3T3 cell line. - The chitosan-based nanocomposite films were prepared from methylcellulose/PEG/chitosan-based nanoparticles in chitosan. These biopolymer films exhibited mechanical and barrier characteristics, high antibacterial, antifungal, antioxidant and UV-protective activity and serve as time–temperature indicators. - 2 Article was published on ISI international jounal Carbohydrate polymers. - Contributed to training 01 bachelor in Chemistry. - Project improved scientific cooperation between Institute of Chemistry and People Friendship University of Russia.
Novelty and actuality and scientific meaningfulness of the results	The project focused on the synthesis of chitosan-triazole derivatives using the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC), followed by the DCC/DMAP-mediated amidation reaction of chitosan-triazoles with ciprofloxacin to afforded the chitosan-triazole-ciprofloxacin conjugates. These conjugates displayed potent antibacterial activities, which is the same or even higher than that of ciprofloxacin. The chitosan-triazole-ciprofloxacin conjugates did not release ciprofloxacin during at least 80 h. The nanoparticles based on chitosan-triazole-ciprofloxacin released ciprofloxacin 30-35% within 50 h, meanwhile nanoparticles based on chitosan-triazole-betaine-ciprofloxacin released ciprofloxacin 100% in 25 h. These results revealed that the chitosan-triazole-ciprofloxacin conjugates are biocompatible biodegradable systems, which are capable for targeted delivery of fluoroquinolones. The project had also studied on the synthesis of water-soluble triazole-chitin derivative and its nanoparticles. The triazole-chitin derivative and its nanoparticles are characterized by a high in vitro antibacterial activity, which is the same or even higher than that of commercial antibiotic ampicillin and gentamicin. Moreover, they are non-toxic against NIH 3T3 cell line. Moreover, the chitosan-based nanocomposite films were successfully prepared from methylcellulose/PEG/chitosan-based nanoparticles in chitosan. These biopolymer films exhibited mechanical and barrier characteristics, high antibacterial, antifungal, antioxidant and UV-protective activity and serve as time–temperature indicators.
Products of the project	- Scientific papers in referred journals: 2 articles in international jounals ISI were published: 1) Andreii S. Kritchenkov, Anton R. Egorov, Rimma A. Abramovich, Aleh V. Kurliuk, Tatsiana V. Shakola, Ekaterina K. Kultyshkina, Moises J. Ballesteros Meza, Anastasia V. Pavlova, Elena P. Suchkova, Giang Le Nhat Thuy, Nguyen Van Tuyen, Victor N. Khrustalev. Water-soluble triazole chitin derivative and its based nanoparticles: Synthesis, characterization, catalytic and antibacterial properties. Carbohydrate Polymers, 2021, 257, 117593. (10.1016/j.carbpol.2020.117593, Q1, ISI, IF = 10.7). 2) Andreii S. Kritchenkov, Anton R. Egorov, Olga V. Volkov, Alexey A. Artemjev, Aleh V. Kurliuk, Tuan Anh Le, Hong Hieu Truong, Giang Le-Nhat-Thuy, Thanh Van Tran Thi, Nguyen Van Tuyen, Victor N. Khrustalev. Novel biopolymer-based nanocomposite food coatings that exhibit active and smart properties due to a single type of nanoparticles. Food Chemistry 2021, 343, 128676 (10.1016/j.foodchem.2020.128676, Q1, ISI, IF = 9,2). - Contributed to training 01 bachelor in Chemistry.
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