Development of local anesthetic drug delivery system by administration of organo-silica nanoformulations under ultrasound stimuli: in vitro and in vivo investigations.

The development of local anesthetic (LA) system is the application of commercial drug for the pain management that indorses the reversible obstructive mechanism of neural transmission through preventing the innervation process in human peripheral nerves. Ropivacaine (RV) is one of the greatest frequently used LA s with the actions of long-lasting and low-toxicity for the post-operative pain management. In this work, we have approached novel design and development of glycosylated chitosan (GCS) encapsulated mesoporous silica nanoparticles (GCS-MONPs)-based nano-scaffold for sustainable distributions and controlled/supported arrival of stacked RV for targeting sites, which can be activated by either outer ultrasound activating to discharge the payload, foundation on-request and dependable analgesia. The structural and morphology analyses result established that prepared nano-formulations have successful molecular interactions and RV loaded spherical morphological structures. The drug release profile of developed nanostructure with ultrasound-activation has been achieved 50% of drug release in 2 h and 90% of drug release was achieved in 12 h, which displays more controlled release when compared to free RV solution. The in vitro cell compatibility analysis exhibited GCS-MONPs with RV has improved neuron cell survival rates when compared to other samples due to its porous surface and suitable biopolymer proportions. The analysis of ex vitro and in vivo pain relief analysis demonstrated treated animal models have high compatibility with GCS-MONPs@RV, which was confirmed by histomorphology. This developed MONPs based formulations with ultrasound-irradiation gives a prospective technique to clinical agony the board through on-request and dependable help with discomfort.

Effects and mechanism of dexmedetomidine on neuronal cell injury induced by hypoxia-ischemia.

BACKGROUND: The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells. METHODS: PC12 cells exposed to OGD was used to establish ischemia model. The OGD-induced cell injury was evaluated by alterations of cell viability, apoptosis and expressions of apoptosis-associated proteins. Oxidative stress and expressions of neurotrophic factors after OGD and DMED treatments were also explored. The activation of possible involved signaling pathways were studied after OGD and DMED treatments, along with the addition of inhibitors of these pathways. Finally, the effects of DMED on primary neuronal cells were verified according to the alterations of inflammatory cytokines release and oxidative stress. RESULTS: DMED obviously increased cell viability and reduced cell apoptosis as well as ratio of Bax/Bcl-2 in OGD-treated PC12 cells. Then, the OGD-induced changes of LDH, MDA, SOD and GSH-Px as well as decreases of neurotrophic factors were all ameliorated by DMED treatment. Key kinases in Notch/NF-κB signaling pathway were up-regulated by OGD, whereas the up-regulations were decreased by DMED. In addition, inhibitor of Notch or NF-κB could augment the effects of DMED on OGD-induced cell injury. Finally, the protective effects of DMED were verified in primary neuronal cells. CONCLUSION: DMED had protective effect on OGD-induced PC12 cell injury, depending on its anti-apoptotic, anti-oxidative activity and the inhibition of Notch/NF-κB activation. Our findings suggested that DMED could be used as a potential therapeutic drug for cerebral ischemia.

[Effect of propofol upon brain after whole-body hyperthermia in rats].

OBJECTIVE: To investigate the effect of propofol upon acute cerebral insult during whole-body hyperthermia (WBH) in rats. METHODS: Sixty male Wistar rats were randomly divided into 6 groups. All the animals were trained with place navigation test of Morris water maze (MWM) for 5 days pre-study. After training, some rats received anesthesia only but not WBH treatment as control, other rats were anesthetized with intraperitoneal injection of 3.0 ml/kg of chloral hydrate and 100 or 150 mg/kg of propofol followed with WBH process (keeping rat core temperature at 42 degrees C for 30 min). Space memory was checked using spatial probe test 24 h after WBH intervention. Rat brain was then removed in 24 h post-WBH to separate hippocampal regions for the detection of neuronal apoptosis with TUNEL method and ultramicrostructural changes by electron microscope. RESULTS: The escape latency were smaller in groups B0, C0, D0, C and D than that in group B (P < 0.05) while smaller in groups B0, C0, D0 than in groups B, C, D respectively. The amount of apoptotic neurons in hippocampus increased orderly as following with no significant differences in group B0, C0 and D0: group B0, C0, D0 < group D < group C < group B (P < 0.05). The injury degree of neuronal ultramicrostructure in hippocampus in group C after WBH were more severe than that in group D but better than that in group B. CONCLUSION: Propofol alleviates the WBH-induced acute cerebral insult by inhibiting the hippocampal neural apoptosis.