DARU Journal of Pharmaceutical Sciences
Year:2013 | Volume:21 | Issue:4|Papers Count:6

Background: siRNA is a new tool for treatment of diseases such as cancer. However, it cannot be used directly due to rapid degradation in body fluid and blood stream; therefore, vectors are necessary for protection of siRNA against RNases and also for its precise delivery to the target cells. Since viral vector causes cancer and immune response in the host, liposomes are more preferable vectors. Liposome size is an important factor for longer circulation time. Extrusion minimizes the liposome size; however, it leads to less liposome encapsulation. Moreover, it changes structure of asymmetric liposomes.Findings: Here, ethanol treatment is introduced as a method of liposome size optimization that significantly decreases the liposome size without any effect on liposome encapsulation and its asymmetric structure formulation. For this, after liposome formation while there is some ether in solution, ethanol was added to fresh liposomes (25 and 30 percent of total liposomes volume) and liposomes were incubated at room temperature with mild agitation for 20 minutes. Finally, the extra ethanol and ether were removed by dialysis.Conclusion: Utilizing this method the liposome size was successfully decreased about 100 nm. The size of optimized liposomes (200 nm) is quite suitable for in vivo target delivery.

Background and the purpose of the study: There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.Methods: The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.Results: Although the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2- (2-chloro-6-methoxyphenoxy) acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4, 5- dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC50 values=7.56–25.04 mg/ml).Conclusion: The results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.

Background and the purpose of the study: Selenium enriched Lactobacillus has been reported as an immunostimulatory agent which can be used to increase the life span of cancer bearing animals. Lactic acid bacteria can reduce selenium ions to elemental selenium nanoparticles (SeNPs) and deposit them in intracellular spaces. In this strategy two known immunostimulators, lactic acid bacteria (LAB) and SeNPs, are concomitantly administered for enhancing of immune responses in cancer bearing mice.Methods: Forty five female inbred BALB/c mice were divided into three groups of tests and control, each containing 15 mice. Test mice were orally administered with SeNP-enriched Lactobacillus brevis or Lactobacillus brevis alone for 3 weeks before tumor induction. After that the administration was followed in three cycles of seven days on/three days off. Control group received phosphate buffer saline (PBS) at same condition. During the study the tumor growth was monitored using caliper method. At the end of study the spleen cell culture was carried out for both NK cytotoxicity assay and cytokines measurement. Delayed type hypersensitivity (DTH) responses were also assayed after 72h of tumor antigen recall. Serum lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels were measured, the livers of mice were removed and prepared for histopathological analysis.Results: High level of IFN-g and IL-17 besides the significant raised in NK cytotoxicity and DTH responses were observed in SeNP-enriched L. brevis administered mice and the extended life span and decrease in the tumor metastasis to liver were also recorded in this group compared to the control mice or L.brevis alone administered mice.Conclusion: Our results suggested that the better prognosis could be achieved by oral administration of SeNP-enriched L. brevis in highly metastatic breast cancer mice model.

Background and the purpose of the study: Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated.Methods: We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-a and TGF-b1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month).Results: A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p<0.001).The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-b1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.Conclusion: This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-a on the effectiveness of silymarin might be used for individualize therapy.

A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm. The proposed method showed excellent linearity at both first and second derivative order in the range of 60–1200 and 1.25–25 mg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found and added concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.

The rapidly growing popularity of methamphetamine use in Iran has posed a new health challenge to the Iranian health sector. Methamphetamine-associated psychosis (MAP) has been frequently reported in Iran in recent years. Although methamphetamine use and MAP are considerable health problems in Iran but there is still a need to conduct epidemiological studies on the prevalence of MAP and its health-related problems. The present paper emphasizes that health policy makers should consider the immediate needs of drug users, their families and the community to be informed about the detrimental health effects associated with MAP. Although MAP could be managed by prescribing benzodiazepines and psychiatric medications but the most effective regime for stabilizing patients with MAP still needs to be studied in Iran. Constant collaborations among psychiatric services and outpatient psychotherapeutic services should be established to successfully manage MAP in Iran. Iranian clinicians especially emergency medicine specialists should be informed about the differences between the two forms of transient and recurrent MAP in order to implement appropriate pharmacological therapies to manage MAP. It is hoped that special training courses are designed and implemented by health policy makers to inform clinicians, health providers and especially emergency medicine specialists to effectively deal with MAP.