Electrosprayed poly(lactic-co-glycolic acid) particles as a promising drug delivery system for the novel JNK inhibitor IQ-1

Elina Kibler; Anastasia Lavrinenko; Ilya Kolesnik; Ksenia Stankevich; Evgeny Bolbasov; Valeriya Kudryavtseva; Andrey Leonov; Igor Schepetkin; Andrei Khlebnikov; Mark T Quinn; Sergei Tverdokhlebov

doi:10.1016/j.eurpolymj.2020.109598

Electrosprayed poly(lactic-co-glycolic acid) particles as a promising drug delivery system for the novel JNK inhibitor IQ-1

Eur Polym J. 2020 Mar 15:127:109598. doi: 10.1016/j.eurpolymj.2020.109598. Epub 2020 Mar 4.

Authors

Elina Kibler¹, Anastasia Lavrinenko¹, Ilya Kolesnik¹, Ksenia Stankevich^{1

2}, Evgeny Bolbasov^{1

3}, Valeriya Kudryavtseva^{1

4}, Andrey Leonov^{1

5}, Igor Schepetkin², Andrei Khlebnikov^{1

6}, Mark T Quinn², Sergei Tverdokhlebov¹

Affiliations

¹ National Research Tomsk Polytechnic University, Tomsk 634050, Russia.
² Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.
³ Microwave Photonics Lab, Institute of Atmospheric Optics V.E. Zuev SB RAS, Tomsk 634055, Russia.
⁴ School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, United Kingdom.
⁵ Institute of High Current Electronics, Siberian Branch, Russian Academy of Sciences, Tomsk 634055, Russia.
⁶ Faculty of Chemistry, National Research Tomsk State University, Tomsk 634050, Russia.

Abstract

Mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), play important role in the regulation of pro-inflammatory cytokine secretion and signaling cascades. Therefore, JNKs are key targets for the treatment of cytokine/JNK-driven diseases. Herein, we developed electrospray poly(lactic-co-glycolic acid) (PLGA) microparticles doped with novel JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1). Optimized electrospray parameters allowed us to produce IQ-1-doped microparticles with round shape, smooth and non-porous surface, and mean diameter of 0.9-1.3 μm. We have shown that IQ-1 was well integrated into the polymer matrix and had a prolonged release in two steps via non-Fickian release. The fabricated particles doped with IQ-1 exhibited anti-inflammatory effects, as indicated by inhibited neutrophil activation and cytokine secretion by human monocytic MonoMac-6 cells. Overall, our study demonstrates that PLGA microparticles doped with a novel JNK inhibitor (IQ-1) could be a promising delivery system for treatment of JNK-mediated diseases.

Keywords: Drug delivery; Electrospray; Poly(lactic-co-glycolic acid); c-Jun N-terminal kinase inhibitor.

Abstract

Grants and funding