DARU Journal of Pharmaceutical Sciences
Year:2013 | Volume:21 | Issue:7|Papers Count:12

Background: Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues.Methods: PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.Results: Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, -11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, -5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 mg) was significantly lower than both free docetaxel (20.2 mg) and unconjugated PLGA nanoparticles (6.2 mg).Conclusion: In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.

Background: Scrophularia striata Boiss. (Scrophulariaceae) is a plant growing in the northeastern part of Iran and being used as a traditional herb for various inflammatory disorders. This study was designed to investigate the protective effects of the Scrophularia striata extract in Ovalbumin (OVA) induced-asthma mice model.Methods: OVA-sensitized mice were intrapritonealy treated with two doses (100 and 200 mg/kg) of the extract on days 8 to 14 separately. Broncoalveolar lavage fluids (BALF) was collected 48 h after the final OVA challenge and then the number of eosinophils and other inflammatory cells were assessed by direct microscopic counting. In addition, total immunoglubolin (Ig) E and OVA-specific IgE levels in serum, IL-4 and IL-5 cytokines in BALF were determined by Enzyme-Linked Immunosorbent Assay. Moreover, phytochemical assay by thin layer chromatography (TLC) and the 2, 2 diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the main compounds and the antioxidant capacity of the plant extract, respectively.Results: The results showed that the main components; including flavonoids, phenolic compounds and phenyl propanoids were presented in the S. striata extract. In addition, the treatment with extract significantly reduced the number of inflammatory cells and suppressed T-helper 2 (Th2) cytokines including IL-4 and IL-5 in BALF. Also, total IgE and OVA-specific IgE levels in the serum decreased.Conclusion: Collectively, it is concluded that the extract has the potential to modulate the Th2 cytokines and could be used as immunomodulatory agent in the treatment of allergic asthma.

Background and purpose of the study: Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn 3+) clusters. Methods: In this study equated Gdn3+clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs.The amount of loaded gadolinium ion into the MWCNTs was quantified by inductively coupled plasma (ICP) method. To improve water solubility and biocompatibility of the system, the complexes were functionalized using diamine-terminated oligomeric poly (ethylene glycol) via a thermal reaction method.Results: Gdn3+loaded PEGylated oxidized CNTs (Gdn3+@CNTs-PEG) is freely soluble in water and stable in phosphate buffer saline having particle size of about 200 nm. Transmission electron microscopy (TEM) images clearly showed formation of PEGylated CNTs. MRI analysis showed that the prepared solution represents 10% more signal intensity even in half concentration of Gd3+in comparison with commerciality available contrasting agent Magnevistâ. In addition hydrophilic layer of PEG at the surface of CNTs could prepare stealth nanoparticles to escape RES.Conclusion: It was shown that Gdn3+@CNTs-PEG was capable to accumulate in tumors through enhanced permeability and retention effect. Moreover this system has a potential for early detection of diseases or tumors at the initial stages.

Background: The marine environment is a unique source of bioactive natural products, of which Sargassum muticum (Yendo) Fensholt is an important brown algae distributed in Jeju Island, Korea. S. muticum is a traditional Korean food stuff and has pharmacological functions including anti-inflammatory effects. However, the active ingredients from S. muticum have not been characterized.Methods: Bioguided fractionation of the ethanolic extract of S. muticum, collected from Jeju island, led to the isolation of a norisoprenoid. Its structure was determined by analysis of the spectroscopic data. In vitro anti-inflammatory activity and mechanisms of action of this compound were examined using lipopolysaccharide (LPS) -stimulated RAW 264.7 cells through ELISA assays and Western blot analysis.Results: Apo-9¢-fucoxanthinone, belonging to the norisoprenoid family were identified. Apo-9¢-fucoxanthinone effectively suppressed LPS-induced nitric oxide (NO) and prostaglandin E2(PGE2) production. This compound also exerted their anti-inflammatory actions by down-regulating of NF-kB activation via suppression of IkB-a in macrophages.Conclusions: This is the first report describing effective anti-inflammatory activity for apo-9¢-fucoxanthinone¢-fucoxanthnone isolated from S. muticum. Apo-9¢-fucoxanthinonemay be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies.

Background: Pain following surgical removal of impacted molars has remained an important concern among practitioners. Various protocols have been proposed to reduce postoperative pain. However, each one has special side effects and limitations. As green tea possesses anti-inflammatory and antibacterial properties, the aim of the current study was to evaluate the effectiveness of green tea mouthwash in controlling postoperative pain.Materials and methods: In a study with split-mouth and double blind design, 44 patients in need of bilateral removal of impacted third molars underwent randomized surgical extraction; following one surgery patients rinsed with a green tea mouthwash from the first to seventh postoperative day and after other extraction rinsed with placebo mouthwash in the same duration. Both patients and surgeon were blinded to the type of mouthwash. The predictor variable was type of mouthwash and primary outcome variable was postoperative pain measured by visual analogue scale (VAS) during first week after surgery. In addition, number of analgesics patients used after surgery recorded. To measure the effect of green tea mouthwash, repeated measures test with confidence interval of 95% was performed.Results: Total of 43 patients with mean age of 24 years underwent total of 86 surgeries. VAS value had no statistically difference prior rinsing among groups (P-value>0.05). However, the mean value of VAS following rinsing with green tea was statistically lower than placebo in postoperative days of 3–7 (P-value<0.05). In addition, while rinsing with green tea, patients took significantly lower number of analgesics after surgery (P-value<0.05). No side effects reported.Conclusion: Green tea mouthwash could be an appropriate and safe choice to control postoperative pain after third molar surgery.

Nuggehally R Srinivas Dear editor-in-chief The recently published article in the esteemed journal entitled “Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution” [1], describes an in-depth research pertaining to the formulation attributes of lumefantrine, an important ani-malarial drug, to enhance its in vitro dissolution and thereby improving its bioavailability upon oral administration. As discussed by authors’ poor solubility of novel chemical entities (NCEs) leads to lack of in vivo translation of the promising in vitro attributes of NCEs because they fail to achieve adequate exposure needed to modulate the target or receptors under in vivo conditions [1]. Since lumefantrine has a low and variable bioavailability dependent on the food intake, it is extremely challenging to maintain the threshold levels of the drug needed to combat malarial infections [2].

A poly (lactide-co-glycolide) (PLGA) implant was used to control the release profile of leuprolide acetate (LA) drug. The system is an in-situ polymeric precipitation system. And the formulation consisted of PLGA polymer, LA drug and N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was injected into PBS solution for in-vitro studies and then it was administered to the animal models (female rats) for in-vivo release studies. The release profiles of leuprolide acetate were measured by UV spectrophotometry for a period of 28 days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in-vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72 hours. However, the rate of LA release was slower in-vivo. This might be attributed to the limited diffusion process of solvent and the drug molecules. This could be due to presence of an additional pressure caused by the surrounding tissue and also the presence of small amount of water between cells in the subcutaneous site. Cross-section and surface of the implants were studied via scanning electron microscopy. Morphology of both in-vitro and in-vivo implants confirmed the release behaviours. No toxicity effects were reported in the histopathological assay. Furthermore, the pharmacological analysis showed more inactive ovaries due to release of LA.

Background: Piroxicam (PXM) belongs to the wide class of non-steroidal anti-inflammatory drugs (NSAIDs). PXM has been widely applied in the treatment of rheumatoid arthritis, gonarthrosis, osteoarthritis, backaches, neuralgia, mialgia. In the presented work, a green and benign sample pretreatment method called temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME) was followed with stopped-flow injection spectrofluorimetry (SFIS) for quantitation of PXM in pharmaceutical formulations and biological samples.Methods: Temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME) was applied as an environmentally friendly sample enrichment method to extract and isolate PXM prior to quantitation. Dispersion of 1-hexyl-3-methylimidazolium hexafluorophosphate ([Hmim] [PF6]) ionic liquid (IL) through the sample aqueous solution was performed by applying a relatively high temperature. PXM was extracted into the extractor, and after phase separation, PXM in the final solution was determined by stopped-flow injection spectrofluorimetry (SFIS).Results and Major Conclusion: Different factors affecting the designed method such as IL amount, diluting agent, pH and temperature were investigated in details and optimized. The method provided a linear dynamic range of 0.2-150 mg l-1, a limit of detection (LOD) of 0.046 mg l-1 and a relative standard deviation (RSD) of 3.1%. Furthermore, in order to demonstrate the analytical applicability of the recommended method, it was applied for quantitation of PXM in real samples.

Background: There are several plants have been used worldwide in the folk medicine with high incidence for treatment of human disorders, of which Lythrum salicaria belongs to the Lythraceae family has traditionally reputation for some medicinal usage and recently many biological and pharmacological activity of the plant have been studied.Methods: In this study, microscopic characterizations of the aerial parts of the plant were determined. Moreover, the plant extract (aqueous methanol 80%) was subjected to an anti-diabetic activity test (in a rat model of streptozocin induced diabetes), anti-Helicobacter pylori (using disc diffusion method) along with antioxidant activity against DPPH (stable free radical) tests. Besides, total flavonoids, phenols, tannins, as well as polysaccharides contents have been assessed using spectroscopic methods.Results: The microscopic properties of the plant fragments revealed anomocytic stomata, conical shape trichomes, and abundant spherical pollen grains as a characteristic pattern for the aerial parts of the plant. The extract of the plant at concentration of 15 g/kg showed mild lowering activity on blood glucose level to 12.6% and 7.3% after 2 and 3 h of administration. Additionally, clinically isolated H. pylori strain was inhibited with the plant extract at concentration of 500 mg/mL (zone of inhibition: 17±0.08 mm). Moreover, IC50 values for DPPH inhibition of the plant extract, vitamin E, BHA were examined as 13.5, 14.2, and 7.8 mg/mL, respectively. Total flavonoids, phenols, tannin, and polysaccharides contents of the extract were successfully evaluated as 5.8±0.4 mg QE/mg EXT, 331±3.7 mg GAE/mg EXT, 340±2.3 mg TAE/mg EXT, 21±0.2 mg GE/mg EXT, respectively.Conclusions: The results suggested that L. salicaria has low anti-diabetic and anti-Helicobacter pylori effects, but high antioxidant activity, just the same as positive standard (vitamin E), which might be attributed to the high content of phenolic compounds in the extract.

Iran in recent decade faced several regional and international sanctions in foreign trade, financial and banking services. Iran national pharmaceutical industry has always played a major role in providing medicines to the Iranian patients. However, following the sanctions it has faced profound difficulties for importing of both finished products and pharmaceutical raw materials. Although medicines are exempted from sanctions, due to restriction on money transaction and proper insurance Iranian pharmaceutical companies have to pay cash in advance for imports of medicines and raw materials or to secure offshore funds at very high risks. Current situation in Iran pharmaceutical market confirms that the sanctions against Iran are affecting ordinary citizens and national health sector which resulted to reduction of availability of lifesaving medicines in the local market and has caused increasing pain and suffering for Iranian patients.

Letter to the editor Tramadol is nowadays one of the most commonly abused drugs in Iran. In our country, few emergency physicians have never visited a tramadol-intoxicated patient referring after overdose or with side effects of its use. One of the complications of tramadol use, abuse, or overdose is seizure [1-4]. It has been shown that the tramadol-induced seizures are not dose-dependent [5].

Stuttering is a complex speech disorder. There are two forms of stuttering: developmental stuttering and acquired stuttering. Developmental stuttering is a disorder of early childhood but acquired stuttering can develop at any age. Some medications can induce or deteriorate stuttering as an adverse effect. There are several reports of stuttering due to psychotropic drugs. Memantine, a glutamate antagonist used in the treatment of Alzheimer’s disease, has also been studied for the treatment of autism spectrum disorders. This report presents deterioration of stuttering and speech problemin two children with autistic disorder who were receiving memantine. Based on our knowledge, this is the first time these adverse drug reactions have been attributed to memantine. In conclusion clinicians should consider that speech problems including stuttering may be due to the consumption of memantine, especially, in children may be a side effect of memantine especially in children.