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Nanofibrous core-sheath nanocomposite dual drug delivery system based on poly(vinyl alcohol) (PVA)/chitosan/lidocaine hydrochloride loaded with gelatin nanoparticles were successfully prepared by the electrospinning method. Gelatin nanoparticles were prepared by nanoprecipitation and were then loaded with erythromycin antibiotic agent with the average particle size of ∼175 nm. The morphology of gelatin nanoparticles observed by field emission scanning electron microscopy (FE-SEM) was shown to be optimal at the concentration of 1.25 wt % of gelatin in aqueous phase by addition of 20 µL of glutaraldehyde 5% as the crosslinking agent. The nanoparticles were also characterized by dynamic light scattering, zeta potential measurement, and Fourier transform infrared spectroscopy (FTIR). The best bead free morphology for the PVA/chitosan nanofibrous mats were obtained at the solution weight ratio of 96/4. The nanofibrous mats were analyzed by swelling studies, FTIR and antibacterial tests. In vitro dual release profile of the core-sheath nanofibers was also studied within 72 h and showed the release efficiency equal to 84.69 and 75.13% for lidocaine hydrochloride and erythromycin, respectively. According to release exponent n, the release of lidocaine hydrochloride from the sheath part of the matrix is quasi-Fickian diffusion mechanism, while the release of erythromycin is based on anomalous or non-Fickian mechanisms.

Objective-Reactive oxygen species (ROS) integrate cellular signaling pathways involved in aortic smooth muscle cell (SMC) proliferation and migration associated with atherosclerosis. However, the effect of subcellular localization of ROS on SMC mitogenic signaling is not yet fully understood. Methods and Results-We used superoxide dismutase (SOD)-deficient mouse aortic SMCs to address the role of subcellular ROS localization on SMC phenotype and mitogenic signaling. Compared with wild-type, a 54% decrease in total SOD activity (Ϸ50% decrease in SOD1 protein levels) and a 42% reduction in SOD2 activity (Ϸ50% decrease in SOD2 protein levels) were observed in SOD1 ϩ/Ϫ and SOD2 ϩ/Ϫ SMCs, respectively. Consistent with this, basal and thrombin-induced superoxide levels increased in these SMCs. SOD1ϩ/Ϫ and SOD2 ϩ/Ϫ SMCs exhibit increased basal proliferation and enhanced [3 H]-thymidine and [ 3 H]-leucine incorporation in basal and thrombin-stimulated conditions. Our results indicate preferential activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases in SOD1 ϩ/Ϫ and janus kinase/signal transducer and activator of transcriptase (JAK/STAT) pathway in SOD2 ϩ/Ϫ SMCs. Pharmacological inhibitors of ERK1/2 p38 and JAK2 confirm the SOD genotypedependent SMC proliferation. Conclusions-Our results suggest that SOD1 and SOD2 regulate SMC quiescence by suppressing divergent mitogenic signaling pathways, and dysregulation of these enzymes under pathophysiological conditions may lead to SMC hyperplasia and hypertrophy. Key Words: ROS Ⅲ SMC Ⅲ thrombin Ⅲ SOD Ⅲ cell signaling S mooth muscle cells (SMCs) are characterized by marked plasticity in their proliferative potential and differentiation status. As the primary constituents of the arterial media, they provide mechanical support for blood vessels and participate in regulation of vasomotor tone. In addition, SMCs contribute to neointimal formation after vascular injury and during atherosclerotic lesion progression in humans. In advanced atherosclerotic lesions, SMCs are prone to apoptosis and release proteolytic enzymes such as matrix metalloproteinases that may contribute to plaque instability. The remarkable diversity of SMC phenotype and function is determined in large part through regulatory cues in the extracellular microenvironment and interactions among intracellular signaling pathways. In addition, SMC phenotypes are modified over time by the accumulation of injuries to cellular macromolecules. See page 887Reactive oxygen species (ROS) are key components for integration of SMC signaling events, whereas at the same time, they are major contributors to the degradation of cellular function through their interactions with proteins and structural components of the cell. Exogenous ROS are potent stimuli for activation of SMC signaling and mitogenesis, 1 although in high (but physiological) concentrations, they may induce DNA damage and mitochondrial dysfunction. 2 SMCs have several intrinsic mechanisms for generating ROS, the majo...

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Taguchi-optimized “hybrid micromixer” has been proposed which can be utilized in a wide range of chemical and biological applications.