ABSTRACT
Wound healing is a complex process and an ongoing challenge for modern medicine. Herein, we present the results of study of structure and properties of ferroelectric composite polymer membranes for wound healing. Membranes were fabricated by electrospinning from a solution of vinylidene fluoride/tetrafluoroethylene copolymer (VDF-TeFE) and polyvinylpyrrolidone (PVP) in dimethylformamide (DMF). The effects of the PVP content on the viscosity and conductivity of the spinning solution, DMF concentration, chemical composition, crystal structure, and conformation of VDF-TeFE macromolecules in the fabricated materials were studied. It was found that as PVP amount increased, the viscosity and conductivity of the spinning solutions decreased, resulting in thinner fibers. Using FTIR and XRD methods, it was shown that if the PVP content was lower than 50 wt %, the VDF-TeFE copolymer adopted a flat zigzag conformation (TTT conformation) and crystalline phases with ferroelectric properties were formed. Gas chromatography results indicated that an increase in the PVP concentration led to a higher residual amount of DMF in the material, causing cytotoxic effects on 3T3L1 fibroblasts. In vivo studies demonstrated that compared to classical gauze dressings impregnated with a solution of an antibacterial agent, ferroelectric composite membranes with 15 wt % PVP provided better conditions for the healing of purulent wounds.
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.
