Goreninskii, Semen Igorevich

Kovrizhina, Anastasia Ruslanovna

Lavrinenko, A. K.

Stankevich, Ksenia Sergeevna

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 Секция 7.  Химия и химическая технология на иностранном языке529DOPING PCL SCAFFOLDS WITH NOVEL JNK INHIBITORS TO IMPART ANTI-INFLAMMATORY PROPERTIESA.K. Lavrinenko, K.S. Stankevich, S.I. Goreninskii, A.R. KovrizhinaScientific advisers – Dr., Professor Victor Filimonov; Ph.D., Associate Professor S.I. TverdokhlebovNational Research Tomsk Polytechnic University 634050, Russia, Tomsk, 30 Lenin Avenue, lav.asy@mail.ruCompounds with 11H-indeno[1,2-b]quinoxal-in-11-one scaffold – IQ–1 and IQ–1E (Fig. 1) were recently identified and characterized as potent C-Jun N-terminal kinase (JNK) inhibitors [1]. JNKs play important role in the pathogenesis of numerous dis-eases including rheumatoid arthritis, insulin resis-tance, cancer, Alzheimer's, and Parkinson's diseases [2, 3]. In particular, they regulate pro-inflammatory cytokine secretion and signaling cascades that lead to inflammation and disfunction [4]. Therefore, JNKs are attractive targets for the treatment of cyto-kine driven diseases. However, poor solubility in water and or-ganic solvents affects bioavailability of IQ–1 and IQ–1E and limits their application. In order to solve this issue, we fabricated poly(ε-caprolac-tone)-based scaffolds doped with IQ–1 (PCL-IQ-1) and IQ–1E (PCL-IQ-1E) via electrospinning using 1,1,1,3,3,3-hexafluoro-2-propanol as a common solvent [5]. All scaffolds were characterized by mi-cron-sized fibers with unimodal diameter dis-tribution and smooth surface. The release of compounds from fabricated scaffolds into the aqueous medium was investigated. The re-lease profile had two steps: burst release due to compound desorption from the surface, followed by sustained release attributed to diffusion into the medium. Commonly used kinetic models were applied to describe the release of IQ–1 and IQ–1E from scaffolds (Table 1). The Higuchi equation was used to calculate the release rate constants (kH), as this model best described the experimental data. Using the Ritger-Peppas model [exponent value (n)], we determined that compound release was controlled by diffusion and swelling, in the case of IQ–1, and only by Fickian diffusion, in the case of IQ–1E [5].Being incorporated in PCL scaffold, IQ–1 and IQ–1E saved the ability to inhibit inflammatory responses. For instance, obtained scaffolds could suppress human neutrophil activation and inhibit inflammatory cytokine production by MonoMac-6 cells. Overall, the obtained results demonstrated that PCL scaffolds doped with JNK inhibitors IQ–1 and IQ–1E could be a promising drug delivery sys-tem that could find application in the treatment of inflammatory diseases.The research was supported in part by United States Department of State Fulbright Visiting Re-searcher Program (Grant ID PS00261116) and the Tomsk Polytechnic University Competitiveness En-hancement Program. Fig. 1.		Structures	of	JNK	inhibitors:11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1), 11H-inde-no[1,2-b]quinoxalin-11-one O-(O-ethylcarboxymethyl) oxime (IQ-1E)Table 1. Values of regression coefficients (R2) for the kinetic models applied to describe the release of the IQ–1 and IQ–1E from the fabricated scaffoldsMathematical model Zero-order First-order Higuchi model Ritger-Peppas modelEquation [5] f = k0 t f = 1 – e–k1 t f = kH t0.5 f = kp tnPCL-IQ-1 0.8963 0.9132 0.9921 (kH = 1.38) 0.9002 (n = 0.53)PCL-IQ-1E 0.9494 0.9870 0.9953 (kH = 3.91) 0.9464 (n = 0.31)XXI Международная конференция «Химия и химическая технология в XXI веке»530References1.	 Schepetkin	I.A.,	Khlebnikov	A.I.,	Potapov	A.S.,	Kovrizhina	 A.R.,	 Matveevskaya	 V.V.,	 Belyanin	M.L.,	 Atochin	 D.N.,	 Zanoza	 S.O.,	 Gaidarzhy	N.M.,	Lyakhov	S.A.,	Kirpotina	L.N.,	Quinn	M.T.	//	 European	 Journal	 of	 Medicinal	 Chemistry,	2019.– V.161.– P.179–191.2	 Solinas	G.,	 Becattini	 B.	 //	Molecular	Metabo-lism, 2017.– V.6.– P.174–184.3	 Koch	P.,	Gehringer	M.,	Laufer	S.A.	//	Journal	of	Medicinal Chemistry, 2015.– V.58.– P.72–95.4	 Cuenda	A.,	 Rousseau	 S.	 //	 Biochimica	 et	 Bio-physica	Acta	(BBA)	–	Molecular	Cell	Research-Biochim., 2007.– V.1773.– P.1358–1375.5	 Stankevich	 K.S.,	 Schepetkin	 I.A.,	 Goreninskii	S.I.,	Lavrinenko	A.K.,	Bolbasov	E.N.,	Kovrizhi-na	 A.R.,	 Kirpotina	 L.N.,	 Filimonov	 V.D.,	 Kh-lebnikov	 A.I.,	 Tverdokhlebov	 S.I.,	 Quinn	 M.T.	//	 ACS	 Biomaterials	 Science	 &	 Engineering,	2019.– V.5.– P.5990–5999.DIAZONIUM-FUNCTIONALIZED LASER-IRRADIATED GRAPHENE AS A MATERIAL FOR FLEXIBLE AND WEARABLE ELECTRONICSA. Lipovka, A. Khalelov, P. Postnikov, E. Dorozhko, E. SheremetScientific advisor – Ph.D., professor R. RodriguezNational Research Tomsk Polytechnic University 634050, Russia, Tomsk, 30 Lenin Avenue, aal26@tpu.ru Graphene and carbon nanostructures are wide-ly spread nowadays for the use in electronic devic-es fabrication. However, graphene itself could be strained to use for the aims of flexible electronics and the Internet of Things due to the poor dispers-ibility in solvents (except the toxic ones) and its bad reinforcement to polymers. In this regard, a mate-rial capable to overcome these issues is one of the graphene derivatives – graphene oxide (GO). GO forms stable water and ethanolic suspensions and is convenient to be used in water-processable depo-sition techniques on arbitrary substrates. Multiple ways, which are globally divided into thermal and Fig. 1.  

Doping PCL scaffolds with novel JNK inhibitors to impart anti-inflammatory properties

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Doping PCL scaffolds with novel JNK inhibitors to impart anti-inflammatory properties

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