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Context: Transdermal local anesthesia is one of the most applied strategies to avoid systemic adverse effects; there is an appealing need for a prolonged local anesthetic that would provide better bioavailability and longer pain relief with a single administration. Objective: Layer-by-layer (LBL) technique was used in this study to explore a nanosized drug delivery system for local anesthetic therapy. Materials and methods: LBL-coated lidocaine-loaded nanostructured lipid nanoparticles (LBL-LA/NLCs) were prepared and characterized in terms of particle size (PS), zeta potential, drug encapsulation efficiency (EE),in vitroskin permeation andin vivolocal anesthetic studies. Results: Evaluation of thein vitroskin permeation andin vivoanesthesia effect illustrated that LBL-LA/NLCs can enhance and prolong the anesthetic effect of LA. Discussion and conclusion: LBL-LA/NLCs could function as a promising drug delivery strategy for overcoming the barrier function of the skin and could deliver anesthetic through the skin with sustained release behavior for local anesthetic therapy. [ABSTRACT FROM AUTHOR]

The neuroprotective role of propofol in transient global and focal cerebral ischemia reperfusion (I/R) animal model has recently been highlighted. However, no studies have conducted to explore the relationship between mitochondrial fission/fusion and I/R injury under the intervention of propofol. Moreover, neuroprotective mechanism of propofol is yet unclear. Culturing primary hippocampal cells were subjected to oxygen-glucose deprivation and re-oxygenation (OGD/R) model, as a model of cerebral I/R in vitro. Methods CCK-8 assay was used to test the effect of propofol on cell viability. We examined the effect of propofol on mitochondrial ultrastructure and mitochondrial fission evoked by OGD/R with transmission electron microscopy and immunofluorescence assay. To investigate possible neuroprotective mechanisms, the authors then examined whether propofol could inhibit calcium-overload, calcineurin (CaN) activation and the phosphorylation of dynamin-related protein 1 (Drp1) during the period of OGD/R, as well as the combination of Drp1-ser 637 and fission 1 (Fis1) protein by immunofluorescence assay, ELISA and double-labeling immunofluorescence analysis. Finally, the expression of Drp1-ser 637 and Fis1, apoptosis inducing factor (AIF) and cytochrome C (Cyt C) were detected by western blot. When added in culture media during OGD period, propofol (0.1μM-50μM) could alleviate neurons injury and protect mitochondrial ultrastructure, meanwhile inhibit mitochondrial fission. Furthermore, the concentration of intracellular free Ca2+, CaN activition and the phosphorylation of Drp1-ser637 were suppressed, as well as the translocation and combination of Drp1-ser 637 and Fis1. The authors also found that the expression of Cyt C, AIF, Drp1-ser637 and Fis1 were down-regulated. Notably, high dose of propofol (100μM-200μM) were confirmed to decrease the survival of neurons based on results of cell viability. Propofol could inhibit mitochondrial fission and mitochondrial apoptotic pathway evoked by OGD/R in rat hippocampal neurons, which may be via depressing calcium-overload. [ABSTRACT FROM AUTHOR]

Purpose: The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid–polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. Methods: LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Theirin vitroskin permeation was studied using a Franz diffusion cell mounted with depilated mouse skinin vitro. In vivolocal anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Results: Compared with LA-LPs, LA-LPNs showed significantly betterin vitroskin permeation ability andin vivolocal anesthetic effects. Conclusion: The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy. [ABSTRACT FROM PUBLISHER]

The mitochondrial calcium uniporter (MCU) transports Ca from the cytoplasm to the mitochondrial matrix and thus maintains Ca homeostasis. Previous studies have reported that inhibition of MCU by ruthenium red (RR) protects the brain from ischemia/reperfusion (I/R) injury and that mitochondrial fission plays an important role in I/R injury. However, it is still not known whether MCU affects mitochondrial fission. In the present study, treatment with RR was found to decrease the concentration of free calcium in the mitochondria, calcineurin enzyme activity and dynamin-related protein 1 expression, and treatment with spermine was found to have the opposite effect in organisms subjected to occlusion of the middle cerebral artery lasting 2 h followed by 24 h reperfusion. These results indicate that MCU may be related to mitochondrial fission via modulating mitochondrial Ca uptake and this relationship between MCU and mitochondrial fission may protect the brain from I/R injury. [ABSTRACT FROM AUTHOR]

In this paper, Bi 2 S 3 nanospheres with size of 212 nm were prepared by a simple hydrothermal process. The selectively enhanced antibacterial effects of Bi 2 S 3 nanospheres with three classes of ineffective antibiotics, β-lactam (cefuroxime, CXM; cefotaxime, CTX and piperacillin, PIP), quinolone (ciprofloxacin, CIP) and aminoglycoside (gentamicin, GEN) against clinical isolated methicillin-resistant Staphylococcus aureus (MRSA) were investigated for the first time. GEN shows significantly synergistic growth inhibition against MRSA when combined with Bi 2 S 3 nanospheres, while CXM, CTX, PIP and CIP do not. Raman spectroscopy and Z potential studies reveal that Bi 2 S 3 could interact with GEN and the combination showed small electronegativity, which probably induced the increase of GEN content in cytoplasm of bacteria. Furthermore, the combination of Bi 2 S 3 nanospheres and GEN can destroy the bacterial membrane function and induce more bactericidal reactive oxygen generation than that of Bi 2 S 3 or GEN alone. The cytotoxicity test indicates that the combination of Bi 2 S 3 and GEN presented low toxicity to human normal hepatocyte L02. This work shows that Bi 2 S 3 nanospheres can be used to enhance the action of ineffective antibiotic GEN against MRSA, thus strengthening the antibiotic capacity for fighting MRSA infections. [ABSTRACT FROM AUTHOR]