International Journal of Pharmaceutical Sciences and Drug Research

129-137

Authors: J. Balasubramanian1*, T. Sravanthi2, V. Sujitha2

The aim of the present review provides the relationship between therapeutic nanoparticles and mononuclear phagocytic system. Reticuloendothelial system (RES) represents a group of cells having the ability to take up and sequester inert particles and vital dyes. This includes macrophages and macrophage precursors, specialized endothelial cell lining the sinusoids of the liver, spleen and bone marrow, and the reticular cell of the lymphatic tissue (macrophages) and of the bone morrow (fibroblast). Nanoparticles are rapidly sequestered and retained by the organs comprising of the reticuloendothelial system (RES), mainly the liver, spleen and the bone marrow. Thus, targeting of the nanoparticles to the reticuloendothelial system (RES) is much simpler than to any other organ. In the liver, the particles are mainly retained by the scavenging periportal and midzonal Kupffer cells, while the hepatocytes and liver endothelial cells may play a secondary role under special pathophysiological conditions or for special physic- chemical characteristics of particles. The clearance of conventional nanoparticles has been proposed to occur by uptake of the nanoparticles by the reticuloendothelial system (RES). The mononuclear phagocytic system uptake of nanoparticles results in their rapid removal from the blood and accumulation in tissues involved in the RES, such as the liver and spleen. Uptake by the RES usually results in irreversible sequestering of the encapsulated drug in the RES, were it can be degraded. In addition, the uptake of the nanoparticles by the RES may result in acute impairment of the mononuclear phagocytic system and toxicity. Sterically stabilized nanoparticles, such as STEALTH nanoparticles, prolong the duration of exposure of the encapsulated nanoparticles in the systemic circulation. The presence of the PEG coating on the outside of the nanoparticles does not prevent uptake by the reticuloendothelial system, but simply reduces the rate of uptake.

143-150

Authors: Sameh S. Zaghlool1*, Basim A. Shehata2, Ali A. Abo-Seif1, Hekma A. Abd El-Latif3

Gastric ulcer is one of the most serious diseases over wide the world. There are many drugs used for the treatment of gastric ulcer, but most of these produce several adverse reactions. This study aims to investigate the protective effects of extracts of Ginger and Marshmallow on pyloric ligation-induced gastric ulcer in rats. Animals were divided into 5 Groups; a normal control group, an ulcer control group, a standard treatment group receiving famotidine (20 mg/kg), and two treatment groups receiving Ginger (100 mg/kg) and Marshmallow (100 mg/kg). Treatments were given orally for 14 days. On the 15th day, animals were subjected to pyloric ligation except for the normal control group. Four hours later, rat stomachs were excised and gastric juice and blood samples were collected. Pyloric ligation caused significant elevations in ulcer number, ulcer index, gastric volume, titratble acidity, acid output, mucin content and peptic activity, accompanied by significant decreases in blood superoxide dismutase activity (SOD) activity and gastric mucosal nitric oxide (NO) and glutathione (GSH) contents. In addition, elevations in gastric mucosal lipid peroxide and histamine contents were observed. Pretreatment with famotidine, ginger or marshmallow significantly corrected all blood and tissue parameters by varying degrees. Famotidine, ginger and marshmallow may protect against pyloric ligation-induced peptic ulcer in rats, being promising for further clinical trials.

157-162

Authors: Pallavi Thakur1, Raman Chawla1*, Ankita Singh Chakotiya1, Raghav Nagpal1, Ankit Tanwar1, Rajeev Goel1, Alka Narula2, Rajesh Arora3, Rakesh K. Sharma1

The herbal extracts of Camellia sinensis (Cs) and Andrographis paniculata (Ap) with standard F/P ratio (flavonoid/ polyphenol) of 0.26-0.27 were used for evaluation of anti-microbial efficacy against Vancomycin Resistant Enterococci (VRE). The bioactivity fingerprints useful for standardizing both extracts were found to be coherent with respect to their Diphenyl picryl hydrazyl radical scavenging potential (IC50 = ~ 30µg/ml). In vitro efficacy analysis of Cs and Ap extracts using exponentially growing culture of VRE revealed Minimum Inhibitory Concentration (MIC) as 200µg/mL and 50µg/mL respectively. The comparative analysis of their Minimum Bactericidal Concentration (MBC) revealed that 5X concentration of Cs as against 10X concentration of Ap was required to achieve zero microbial count. Such analysis indicated that both extracts would be useful for future analysis. In vivo pre-clinical evaluation studies are underway for utilization of identified herbal leads for trials on humans.

168-171

Authors: Meghraj Singh Baghel*, Kavita Goswami

Cancer is referred as uncontrolled growth of abnormal cell mass. Out of the several types of cancer, prostate cancer (PC) has become a major public health problem in men worldwide. Bcl-2 and p27 proteins are important regulatory molecules of cell cycle. Failure of cell cycle regulation leads to uncontrolled cell proliferation and causes cancer. For designing an effective structural based targeted drug, the assessment of protein-protein and protein-ligand interaction is indispensable. Therefore for treatment of PC, we selected a ribosome inactivating protein, Ricin, for assessment of its therapeutic nature. In the present work through CLUSTAL-W phylogenetic analysis, we found that Bcl-2 protein was found more conserved than p27. Further Bcl-2 was selected as target molecule for docking study with Ricin protein and other chemically synthetic inhibitor molecules i.e. 2-difluoromethylornithine (DFMO) and Sarcosine, as lead molecule. Through HEX5.1 docking software docking was performed between targeted receptor and lead molecules. Energy maximum (Emax= -93.12) and energy minimum (Emin= -163.07) was observed for docking complex of optimised and energy minimised structure of Bcl-2 receptor with Ricin, which in turn shows that it is highly stable interaction. On the other hand, for synthetic inhibitors, we found energy maximum (DFMO; Emax= -77.17, Emin= -117.83 and Sarcosine; Emax= -72.23, Emin= -103.00) and energy minimum, which are significant more as compared to Ricin docking complex. Due to ricin docking complex having less energies shows stable interaction with Bcl-2. We also observed that Ricin is less toxic (lesser log P value) as compared to other molecules by toxicity analysis by ADME/TOX server. These evidences show this Ricin could be better drug for PC. Further results are needed to validate by in vitro and in vivo study to make proper elucidation of drug for better PC treatment.

176-181

Authors: T. K. Laha1*, S. Sen1, G. Mishra2

A rapid and sensitive high performance liquid chromatographic method is described for simultaneous determination of duloxetine and its major metabolites, such as 4- hydroxy duloxetine (M7), Glucuronide conjugate of 5-hydroxy-6-methoxy duloxetine (M6) and Glucuronide conjugate of dihydrodiol duloxetine (M12) in rabbit plasma. HPLC analysis was carried out on a µ-Bondapak C18 column (250 mm × 4.6 mm, 5µm particle size) using methanol: phosphate buffer (pH 7.9, 50 mM) (7:3 v/v) as the mobile phase at a flow rate of 1.5 ml/min. Detection was carried out at 224 nm with an UV detector. The above metabolites present in the rabbit plasma were characterized by retro-synthesis followed by NMR and MS study for structure confirmation and finally injected separately into the HPLC system. All the three retention time matches with the metabolites present in the plasma sample.

188-192

Authors: Ayyagari Rama Murthy1*, K. Raghu Babu1, N. A. Vekariya2

Objective of the study was to develop and validate a new rapid, sensitive, reverse phase High Performance Liquid Chromatography technique for the estimation of Olanzapine in bulk and dosage form. Chromatographic separation was achieved on a BDS Hypersil C18, (150 mm × 4.6 mm, 5μm) with a mobile phase of 0.01M Tetra butyl ammonium hydrogen sulphate: Methanol (60:40) v/v. The flow rate was 1.0 ml/min, temperature of the column was maintained at ambient and detection was made at 228 nm. The run time was as short as 10.0 min. The developed method was validated according to the International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision, specificity and robustness. The developed method was linear for Olanzapine from 10 - 80μg/ml and the linear regression obtained was 0.9994. Recovery of Olanzapine was found to be in the range of 99.6 -101.7%. Precision, evaluated by intra- and inter-day assays had relative standard deviation (R.S.D) values within 1.0 %. The ruggedness of the method was validated by performing the analysis by two different analysts and no significant difference in the result was found. Robustness of the method was checked by varying flow rate by 0.2 ml/min and the result was not affected significantly. The analysis of the marketed sample indicated that the method can also be applied to dosage form successfully. The method is precise, accurate, linear, robust and fast. The retention time and run time was very short; hence it is cost effective, making it more economical and rapid. Hence, this method can be used for the analysis of large number of samples.

198-204

Authors: Jasmine Karanjia*

This paper describes two sensitive, accurate and precise chemometric spectrophotometric methods for the simultaneous determination of Cinitapride hydrogen tartarate (CNT) and Pantoprazole sodium (PANTO) in bulk powder and capsules without prior separation. Multivariate calibration chemometric methods are proposed for simultaneous determination of CNT and PANTO. The chemometric methods applied are Principal Component Regression (PCR) and Partial Least Squares (PLS). These approaches are successfully applied to quantify both drugs using the information included in the absorption spectra of appropriate solutions. In these multivariate methods, calibration sets of standard samples composed of different mixtures of CNT and PANTO have been designed. The methods were validated according to The International Conference on Harmonization (ICH) guidelines. The specificity of the proposed methods was tested using laboratory-prepared mixtures. The developed methods were successfully applied for the determination of CNT and PANTO in bulk powder and dosage form combination.