Cancer stem cells (CSCs) have been defined as a unique subpopulation in tumors, endowed with the capacity to initiate tumor progression, and maintain self-renewal as well as metastatic potential. Recently, more evidences strongly indicate the existence of CSCs in solid tumors of wide variety of organs such as breast, brain and stomach. Recent studies suggest that a special subpopulation of gastric cancer cells with specific marker namely CD44, shows spheroid colony formation in serum free media in vitro, as well as tumorigenic capacity in immunodeficient animal model in vivo. In addition, current evidences indicate that one of the major reasons for failure of chemotherapy and radiotherapy is the existence of CSCs with resistant mechanisms against current therapeutic strategies. Growing evidence recommended that pathways which are responsible for regulation of normal stem cell self-renewal and differentiation may also represent regulatory roles in maintenance of cancer cells and CSCs. Two major therapeutic approaches for elimination of CSCs are differentiation therapy and inhibition of important pathways involved in maintenance of CSCs such as notch signaling.It is hypothesized that with inhibition of notch signaling by means of DAPT(gamma-secretase-inhibitor), silencing Ral pathway as well as inducing differentiation by means of all-trance retinoic acid (ATRA) in CD44⁺ gastric cancer stem cells, we can target this small population and eventually eliminate them by sensitizing these cells to chemotherapy and radiotherapy as well as induction of apoptosis in them.

Aphthous stomatitis and oral lichen planus may be found on mucosal surfaces including the gingival, tongue and lips. These conditions frequently require topical corticosteroid medication such as TriamcinoloneAcetonide (TA).Recently, studies showed that divalent inorganic salts such as Zinc Sulphate (ZnSO₄) are recommended for treatment of aphthouse, herpes ulcers and other ulcers in the body. In this study we developed orabase formulation of ZnSO₄ 0.25% and TA 0.1% that is suggested tohavesynergistic effect on ulcer treatment. To achieve this goal, different ratio of bioadhesive polymers such as pectin, gelatin, NaCMC and plastibase were used and the effects of these factors were evaluated on physicochemical properties of the pastes. The in vitrobioadhesive strength, spreadability test and occlusivity strength properties of the Orabase were investigated using new designed device, while swelling behavior was studied in different media, namely, distilled water and simulated salvia solution. TA and ZnSO₄ concentration were determined using HPLC and voltammetry system, respectively. The in vitro drug release was investigated in phosphate buffer (pH=7) at 37°C by Franz diffusion cell. The optimum formulation showed that the increase in NaCMC content and decrease in water content were found to elevate the bioadhesive and occlusivity strength. Also decrease in NaCMC content was found to elevate the drug release rate. Optimum formulation had adhesion strength equal to 131.948 mN/cm², spreadability equal to 0.067 cm, percent of occlusivity strength equal to 53.3% and a swelling index very similar to brand sample (Adcortyl0.1%) in both the distilled water and phosphate buffer. We canclaim that optimum formulation is comparable to brand sample and we suggest that it is a promising and suitable carrier for transmucosal drug delivery system.

The new drug delivery systems have been developed, which can remain in the stomach for prolonged period of time. The effervescent floating tablet is one of these systems. Iron deficiency anaemia is a common disease in the world. Ferrous sulphate is the most common ferrous preparation used to treat and prevent iron deficiency, but it has little bioavailability and several complications. Ferric-maltol complex (FMC) is a ferric compound which doesn't have ferrous complications. In this study FMC was used for preparing effervescent floating tablets that are designed to prolong the gastric residence time of drug, increase drug bioavailability and treat iron deficiency. At first the active ingredient (FMC) was synthesized from maltol and ferric chloride, the formation of complex was confirmed. Eleven tablet formulations were designed using different amounts of gel-forming agents (HPMC K4M, Carbopol 934 P), and effervescent agents (sodium bicarbonate and citric acid). Pre-compression parameters of powder blend (bulk density, tapped density, angel repose, Carr's index, hausner's ratio) were measured; the tablets from each formulation were prepared by direct compression method. Buoyancy study of tablets was investigated. The F3-F11 tablets were selected for further post compression evaluations (thickness, hardness, friability, weight variation, drug content, in vitro dissolution study, swelling ability, drug release mechanism determination). F9, F10, F11 were the most appropriate formulations. They were very similar in consideration of swelling property, total floating time and drug release kinetic & mechanism. Among these three formulations, F11 was selected as the best formulation with more suitable buoyancy behavior. The F11 tablets were able to float immediately and remained buoyant for more than 18 hours. The drug release pattern followed zero order kinetic with non-fickian diffusion. 98.54% of FMC released from F11 floating tablets after 12 hours. Physical stability of F11 tablets was evaluated according to ICH guidelines. This formulation showed no-significant change in physical properties after storage at 40oC and 75% RH for 3months.

A sensitive and selective method using combination of principal component analysis (PCA), artificial neural network (ANN) and UV-Visible spectroscopy has been developed for the simultaneous determination of acetaminophen (AMP) and codeine (COD) in plasma samples. The ANN trained by the back-propagation learning was employed to model the complex non-linear relationship between the PCs extracted from UV-visible spectra of medications and the absorbance values. Optimal ANN model were as follows: Number of input PCs: 6, number of neurons in hidden layer: 5. The linear calibration range was 10-70 μg ml^-1 and 40-700 μg ml^-1, and the detection limit were 0.3 μg ml^-1 and 1.3 μg ml^-1, for AMP and COD, respectively. The results have been compared with those obtained by the HPLC method.

In the recent years, targeted therapy of the neoplastic diseases is a current strategy used by oncologists. Hence, design and discovery of novel targeted anticancer therapeutics is an interesting topic in the current research of medicinal chemistry. A new series of 1,3,4-thiadiazole derivatives were prepared and their anticancer activity was assessed against PC3, SKNMC and HT29 cell lines by application of the MTT assay. Compound 3e with para positioning of the methoxy moiety demonstrated the highest inhibitory potency against PC3 (IC₅₀ = 22.19 ± 2.1 μM) and SKNMC (IC₅₀ = 5.41 ± 0.35 μM) cell lines in this series. This compound rendered a superior cytotoxic activity than imatinib. Compound 3f with ortho positioning of the fluorine displayed the most cytotoxic activity against HT29 cell line compared to other tested derivatives (IC₅₀ = 12.57 ± 0.6 μM). Molecular docking studies on Abl as well as Src tyrosine kinases were also performed and potential hydrogen bindings were observed for ligand-receptor interaction.

A great challenge in using natural polysaccharide as drug delivery system is their fast drug release. The purpose of the present study was to prepare and evaluate chitosan oligosaccharide (CHO)-de-estrifiedtragacanth (DET) core-shell nanoparticles for controled release of water soluble drugs. CHO-DET nanoparticles were prepared by microemulsion method and characterized by FT-IR spectroscopy. Size, zeta potential, loading efficacy, and in vitro drug release were also investigated. Morphology of nanoparticles was evaluated by the scanning electron microscopy. The optimum particles with an average size of 400 nm were prepared. Loading efficacy of nanoparticles in drug/polymer ratios of 1/3.5 and 1/5 was 18.88 ± 3.95 and 17.55 ± 2.13. At the ratio of 1/5, release of 5-FU was sustained and less than 25% of drug was released at pH 7.4 and 11.14% of 5-FU was released at pH 1.5. At ratio of 1/3.5, release rate was faster than ratio of 1/5, and more than 30% of drug was released after 22 h at pH 7.4. drug release for this ratio was 29.14% at stomach pH. These phenomena make CHO-DET core-shell nanoparticles as a great candidate for controlled drug delivery system specially for colon targeted delivery where bacterial flora cleave polysaccharides and release their drug content in colon region.

In published high performance liquid chromatographic (HPLC) methods for analysis of topiramate (TPM) in pharmaceutical dosage forms and raw materials Refractive Index Detector (RID) has been used which is not available in many laboratories and has low sensitivity. We described a new, sensitive and simple HPLC method for determination of topiramate in pharmaceutical forms and In-virto dissolution studies which avoids the use of RID detector. The method is based on derivatization of topiramate and an internal standard by reaction with 4-chloro-7-nitrobenzofurazan (NBD-CL), and reverse-phase chromatography using phenyl column and spectrophotometer detection at 264 nm. A mixture of phosphate buffer (0.05 M) containing triethylamine (0.1% V/V; pH=2.3) and methanol (28:72, V/V) at a flow rate of 2.2 ml/min was used as mobile phase. The analysis performance was studied and the method was shown to be selective and linear for determination of topiramate in pharmaceutical forms and dissolution studies.

Pregabalin (PRG) is a new antiepileptic drug and Aceclofenac (ACE) is a potent non-steroidal anti-inflammatory drug. These drugs in combination are used for treatment of partial seizures and neuropathic pains. A simple and precise assay method by RP-HPLC was developed and validated for estimation of PRG and ACE in Acenac-N tablet. Analyses of commercial tablet, Acenac-N were performed using JASCO Isocratic HPLC system at 248 nm on a reverse phase column HiQ sil C18HS (4.6 × 250 mm, 5μm), a mobile phase; methanol: phosphate buffer (70:30 v/v, PH 3). The validation aspects were selectivity, linearity, precision, accuracy and quantification limit. Linearity, 5-25 μg/mL for PRG and ACE respectively, provided determination coefficients (R²) of 0.998 and 0.994 respectively, for PRG and ACE and proved precise since the RSD% was less than 2%. The recoveries obtained ranged from 99.10% to 100.90% for both of the drugs with RSD% less than 2%. The LOD for PRG and ACE was found to be 0.270 μg/mL and 0.039 μg/mL respectively. The LOQ was found at 0.818 μg/mL and 0.120 μg/mL respectively for PRG and ACE. In this study, the optimization of mobile phase, flow rate, injection volume and wavelength were achieved. The retention time for PRG and ACE was 3.241 and 6.581 min respectively. Drug content of the Acenac-N tablet was found to be 99.53% and 100.12% respectively for PRG and ACE. The method was validated as per the ICH guidelines. This method is precise, accurate and easy to analysis PRG and ACE in tablets.

Diabetes is a metabolic disorder inducing undesirable effects on male reproductive system. Cannabis sativa (C. sativa) is a plant that affects diabetes and decreases blood glucose. The present study was aimed to investigate the effect of Cannabis sativa hydroalcoholic extract on sperm parameters in diabetic rats. Thirty five male Wistar rats (210-240 gr) were divided into five groups: control (distilled water) and four diabetic (60 mg/kg STZ) groups. Diabetic groups were assigned to one diabetic and three experimental groups (receiving 10, 50, and 100 mg/kg extract). Extract was administered interaperitonealy (IP) for 14 days. The animals were weighed and sacrificed at the end of the study. Blood sample was taken and serum testosterone was measured via ELISA method. Also, testes were weighed and sperms were collected from cauda epididymis and analyzed in terms of count, motility and morphology. Histological slides were prepared from testis and seminiferous tubules diameter was determined using Motic camera and software. Data were analyzed using One-way ANOVA method and P<0.05 was considered statistically significant. The mean of blood glucose in experimental groups indicated a significant decrease compared to diabetic group (P=0.00). The mean of sperms count and motility, percentage of sperms with normal morphology, testosterone hormone level, seminiferous tubules diameter, and final body weight in diabetic and experimental groups decreased significantly compared to control group (P=0.00). Cannabis sativa hydroalcoholic extract can induce a moderating effect on hyperglasemia resulting from diabetes, but has no ameliorating effect on diabetic reproductive dysfunctions.