Advanced Pharmaceutical Bulletin

Purpose: Ketamine-propofol combination (ketofol) is being used to provide a safe and effective procedural sedation (PS) in emergency department (ED) and may theoretically have beneficial effects since using lower doses of each drug may result in a reduction of the adverse events of both agents while maintaining optimal conditions for performing procedures. This systematic review was conducted to evaluate the efficacy, advantages and disadvantages of these two drugs for PS. Methods: The PRISMA statement was used for this systematic review. We searched the databases of PubMed, Scopus, ProQuest, Medline (Ovid) from 1990 to August 2017 for randomized clinical trials (RCTs) in which the study population aged ≥18 and was referred to ED. Full-texts of the studies performed in adults that were published in English were reviewed for inclusion. Both authors independently evaluated all studies. Five articles were eligible for the meta-analysis based on their common outcomes. Results: The total number of subjects was 1250, of which 635 were treated with propofol and 615 were treated with ketofol. Although two of the five studies showed a better quality of sedation with ketofol, the other three did not find any significant difference between propofol and ketofol. This systematic review found a lower incidence of respiratory adverse effects in ketofol group than propofol group. Conclusion: Ketamine/propofol mixture (ketofol) has less respiratory adverse effects than propofol alone in ED procedural sedation.

Purpose: Free radicals such as hydroxyl and peroxide are contributing factors to neuronaldestruction in cerebral ischemia. Alpha-lipoic acid (ALA) is one of the potent knownantioxidants. Preparation of ALA niosomes allows IV injection and can increase bioavailabilityand penetration into the central nervous system (CNS).Methods: Film hydration method was used to prepare different niosomes composed of Span®,Tween®, and cholesterol at different molar ratio. ALA and niosome-forming compounds weredissolved in chloroform, before removing the organic solvent by rotary evaporator. Animalswere randomly divided into four groups: Sham, control group, intravenous (IV) injection ofempty niosomes plus intraperitoneal (IP) injection of ALA solution, and finally, IV injectionof ALA niosomes. Rats were subjected to deep anesthesia before inducing cerebral ischemia,then, their internal common carotid arteries were clamped for 15 min and reperfusion wasdone for 30 min. Niosomal ALA was injected intravenously just before declamping.Results: Mean volume diameter of the prepared niosomes was between 4.36 ± 0.82 and 19.95± 1.21 μm in different formulations. Encapsulation efficiency percent (EE%) of ALA in theselected formulation, Span60/Tween60/cholesterol (35:35:30 molar ratio), was 94.5 ± 0.2, and59.27 ± 5.61% of ALA was released after 4h. In the niosomal group, the rate of reduction incomplications of cerebral ischemia such as histopathologic changes and acute damage (fromscore 3 to 1) in CNS was higher than other groups.Conclusion: The obtained results show that niosomes can be used as effective drug deliverysystems for ALA in cerebral ischemia.

Purpose: The expression of miR-146a-5p and miR-193a-5p in colorectal cancer (CRC) is associated with cancer development, metastasis, and reduced survival rate of the tumor-suffered subjects. This examination aimed to assess the impact of these microRNAs (miRNAs) in CRC and their mechanisms in the proliferation and migration of cancer cells. Methods: miR-146a-5p and -193a-5p were transfected into the HT-29 cell line and assessed their impact on metastasis-related genes. The synergistic effects of these miRNAs on migration were evaluated by wound healing approach. To assess the influence of these miRNAs on the proliferation of and apoptosis of cells, the MTT test, annexin V staining test, and DAPI staining test were done. Then, the protein expression of extracellular-signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK) were investigated. Results: miR-146a-5p and-193a-5p could inhibit the CRC cells proliferation, and could synergistically induce apoptosis in CRC cells, and also repressed cell migration, and could reduce p-ERK expression. Conclusion: miR-146a-5p and-193a-5p have an important role in cell viability and proliferation via ERK signaling pathway. Thus, the simultaneous use of these miRNAs may be suggested as a probable therapeutic strategy in this cancer therapy.

Purpose: Accumulating evidence shows the genus of Sambucus exerts a broad spectrum ofmedicinal potencies such as anticancer, antiviral, antibacterial, and antidiabetes. Based on theprevious studies, we hypothesized that bioactive compounds of Sambucus might alter severalbiological systems, including the immune system. Therefore, this study extensively aimed toevaluate the immunomodulatory activities of Sambucus javanica extracts in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/c mouse.Methods: The experimental mice were orally administrated with 2.8 mg.kg-1 BW of DMBA forten times within a month. After that, the mice were treated by S. javanica berries and leavesextracts for 2 weeks. Subsequently, the inflammation rate was evaluated by using flow cytometryanalysis, whereas the necrosis incidences were observed by hematoxylin & eosin staining.Results: Based on the results, we found the expression of tumor necrosis factor alpha (TNF-α)and interferon gamma (IFN-ɣ) were increased however after treated by S. javanica berries andleaves extracts were significantly decreased. In the same way, necrosis incidence was increasedin the DMBA-treated group however it was diminished with S. javanica extracts treatment.Conclusion: Together, these results suggested that S. javanica extracts have immunomodulatoryactivities to suppress inflammation and reduce necrosis incidence in experimental mice.<br />

Nanoparticles (NPs) have been found to be potential targeted and controlled release drug delivery systems. Various drugs can be loaded in the NPs to achieve targeted delivery. Chitosan NPs being biodegradable, biocompatible, less toxic and easy to prepare, are an effective and potential tool for drug delivery. Chitosan is natural biopolymer which can be easily functionalized to obtain the desired targeted results and is also approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration [US FDA]). Various methods for preparation of chitosan NPs include, ionic cross-linking, covalent cross-linking, reverse micellar method, precipitation and emulsion-droplet coalescence method. Chitosan NPs are found to have plethora of applications in drug delivery diagnosis and other biological applications. The key applications include ocular drug delivery, per-oral delivery, pulmonary drug delivery, nasal drug delivery, mucosal drug delivery, gene delivery, buccal drug delivery, vaccine delivery, vaginal drug delivery and cancer therapy. The present review describes the formation of chitosan, synthesis of chitosan NPs and their various applications in drug delivery.