Synergistic effects of citicoline and silymarin nanomicelles in restraint stress-exposed mice.

This study evaluated the effects of citicoline and silymarin nanomicelles (SMnm) in repeated restraint stress (RRS). METHOD: Mice were exposed to RRS for four consecutive days, 2 hrs. daily. On day 5 of the study, SMnm (25 and 50 mg/kg, i.p.) and citicoline (25 and 75 mg/kg), and a combination of them (25 mg/kg, i.p.) were initiated. On day 18, anxiety-like behavior, behavioral despair, and exploratory behavior were evaluated. The prefrontal cortex (PFC) and the hippocampus were dissected measuring brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and tumor necrosis factor-alpha (TNF-α) through Western Blot and ELISA, respectively. RESULTS: In RR-exposed mice, anxiety-like behavior in the elevated plus maze (EPM) was enhanced by reductions in open arm time (OAT%) P < 0.001, and open arm entry (OAE%) P < 0.001. In the forced swimming test (FST), the immobility increased P < 0.001 while the swimming and climbing reduced P < 0.001. In the open field test (OFT), general motor activity was raised P < 0.05. Further, body weights reduced P < 0.001, and tissue BDNF and pCREB expressions decreased P < 0.001 while TNF-α increased P < 0.001. Conversely, SMnm, citicoline and their combination could reduce anxiety-like behavior P < 0.001. The combination group reduced the depressive-like behaviors P < 0.001. Moreover, body weights were restored P < 0.001. Besides, BDNF and pCREB expressions increased while TNF-α reduced, P < 0.001. CONCLUSION: The combination synergistically improved emotion-like behaviors, alleviating the inflammation and upregulating the hippocampal BDNF-mediated CREB signaling pathway.

Diazepam Loaded Solid Lipid Nanoparticles: In Vitro and In Vivo Evaluations.

Purpose: To overcome the side effects of repetitive administration of diazepam (Dzp) besidesgaining benefits from sustaining release of the drug, which contributes to patient compliance,we concentrated on designing and preparing Dzp solid lipid nanoparticles (SLNs). Methods: Using cholesterol (CHOL), stearic acid (SA), and glycerol monostearate (GMS), SLNswere prepared by high shear homogenization technique coupled with sonication. Polysorbate80 (Tween 80) was used as a nonionic surfactant. After modification of prepared SLNs, particlesize, zeta potential, drug-loading efficiency, morphology, and scanning calorimetry, as well asrelease studies were conducted. To increase the stability of desired particles, freeze-drying bycryoprotectant was carried out. In the final stage, In vivo studies were performed by oral (PO)and intraperitoneal (IP) administrations to Wistar male rats. Results: Results indicated that optimized prepared particles were on average 150 nm diameterin spherical shape with 79.06 % loading efficiency and release of more than 85% of the loadeddrug in 24 hours. In vivo investigations also illustrated differences in blood distribution of Dzpafter loading this drug into SLNs. Conclusion: Based on the findings, it seems that drug delivery using SLNs could be anopportunity for solving complications of Dzp therapy in the future.