TY - JOUR
T1 - Electrosprayed poly(lactic-co-glycolic acid) particles as a promising drug delivery system for the novel JNK inhibitor IQ-1
AU - Kibler, Elina
AU - Lavrinenko, Anastasia
AU - Kolesnik, Ilya
AU - Stankevich, Ksenia
AU - Bolbasov, Evgeny
AU - Kudryavtseva, Valeriya
AU - Leonov, Andrey
AU - Schepetkin, Igor
AU - Khlebnikov, Andrei
AU - Quinn, Mark T.
AU - Tverdokhlebov, Sergei
PY - 2020/3/15
Y1 - 2020/3/15
N2 - 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.
AB - 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.
KW - c-Jun N-terminal kinase inhibitor
KW - Drug delivery
KW - Electrospray
KW - Poly(lactic-co-glycolic acid)
UR - http://www.scopus.com/inward/record.url?scp=85081020050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081020050&partnerID=8YFLogxK
U2 - 10.1016/j.eurpolymj.2020.109598
DO - 10.1016/j.eurpolymj.2020.109598
M3 - Article
AN - SCOPUS:85081020050
VL - 127
JO - European Polymer Journal
JF - European Polymer Journal
SN - 0014-3057
M1 - 109598
ER -