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Objective: The aim of the present study is to prepare poloxamer based formulations of meloxicam to evaluate various parameters like pH stability, drug release and in vitro anticancer activities in cell lines with an intention to formulate injectable sustained biodegradable drug delivery system. Method: Various strengths of meloxicam formulations were prepared by using poloxamer 407. Prepared formulations were analyzed for drug content and pH stability by using HPLC. Drug release studies were tested by using USP dissolution testing apparatus. Further, we evaluated in vitro anticancer activity among these formulations by using sulphorhodamine-B (SRB) assay in two leukemia cell lines such as HL-60 and K-562 cell lines. Results: It showed that among all formulations, F1 formulation showed stability at pH 6.8, 7.0 and 7.4. It also showed 60% drug release and exhibited good anti cancer activity in HL-60 cell line with GI 50 <10 µg/ml as similar to adriamycin. Conclusion: Comparing these results, we concluded that F1 formulation showed good anticancer activity in cell lines, therefore further studies are necessary to confirm the mechanism of toxicity action studies. Thus these formulations has a potential to be a sustained release, passive targeted deliver system for meloxicam, with reduced side effects associated with the drug.

A stability indicating simple, selective, accurate high Performance Liquid Chromatographic (HPLC) method was developed and validated for the combined tablet formulation of pyrimethamine & sulphadoxine. Chromatographic separation was optimized by gradient HPLC on a C18 column [Inertsil Silica, 250 x 4.6 mm, 5µ] utilizing a mobile phase of potassium dihydrogen phosphate and acetonitrile taken in the ratio 70:30 at a flow rate of 1.0 ml/min with UV detection at 221nm. The retention time of pyrimethamine and sulphadoxine was 2.77 and 6.57 min respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation, robustness and stress degradation studies. Validation of the method was done in accordance with ICH guidelines for the assay of active ingredients. Thus validated method can be recommended for the routine laboratory analysis.

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INTRODUCTIONHuman DDX3 gene encodes a polypeptide of 662 amino acids and this protein plays an important role in several aspects of RNA metabolism. 1,2 This protein has two clear distinguishable domains comprised of N-terminal DEAD box domain 1 (211-403 residues) and C-terminal helicase domain 2 (411-575 residues). Both domains displayed RecA-like folds comprising a central β-sheet flanked by α-helices connected by a noncanonical linker of 11 amino acids.3 Expression of DDX3 was detected in several tissues such as testis, colon, lung, liver, skeletal muscle, and kidney 2,4 indicating the universal role of DDX3 in cellular homeostasis. Moreover, elevated expression of DDX3 was found in a highly aggressive metastatic breast cancer cell line, MDA-MB-231, as compared with non-metastatic MCF-7 cells, which show its potential role in aggressive breast cancers and associated metastasis. 5,6 We have previously reported that overexpression of DDX3 in immortalized non-turmorigenic MCF10A cells promoted neoplastic transformation as indicated by down regulation of a cell adhesion molecule, E-cadherin.5 Down-regulation of E-cadherin is a common feature of a variety of metastatic epithelial tumors, including those of the lung, breast and prostate cancer.5,7-9 Hypoxic regions of solid tumors were considered to be the primary sites for the generation of the metastatic phenotype and have been demonstrated to be chemo and radio-resistant. [10][11][12][13][14] We have also reported that hypoxia inducible factor (HIF-1) induce the expression of DDX3 in two different breast cell lines by binding directly or indirectly to the hypoxia-response element (HRE) in the DDX3 proximal promoter. 15 On the other hand, a significant down regulation of DDX3 expression is found in hepatocellular carcinoma (HCCs) from the hepatitis B virus (HBV) positive patients, but not from HCV positive in comparison to the corresponding non tumor tissues. 16 In the hepatocellular carcinoma model, DDX3 was found to act as a tumor suppressor by activating the expression of cyclin dependent kinase inhibitor p21 cip1 . 17 Besides cancer, induced expression of DDX3 was also found in HIV-1 infected cells. 18,19 Overall, it suggests that DDX3 is a multifunctional protein and it plays a specific role in regulatory mechanisms and signaling pathways. Apart from embryonic development, this gene is also involved in multiple diseases like HIV, Neuro-degenerative diseases, hepatocellular carcinoma and brain and breast cancer. Several Synthetic compounds have been discovered to inhibit the function of DDX3 by blocking the function of helicase activity. [20][21][22][23][24] Synthetic drugs are those substances that are produced entirely from chemical reactions in a laboratory. Synthetic drugs most often have shown to suppress the immune system by paralyzing the bone marrow. 25,26 Moreover, it takes an average of about 8 to 12 years from the time a cancer drug enters into clinical trials from the research lab.27,28 Therefore, we focused to identify FDA approved drugs against D...