FORMULATION AND EVALUATION OF GLIMEPIRIDE-LOADED LIPOSOMES BY ETHANOLINJECTION METHOD

ABSTRACTObjective: The objective of present study deals with an attempt to formulate Glimepiride in liposomal drug delivery system, in order to maintainsteady state plasma concentration; hence it has to be administered frequently to the patients, because of its short plasma half life. To maintain steadyplasma concentration for longer period of time formulation of controlled drug release system is essential. Liposomal drug delivery system providessustained release of Glimepiride.Methods: Glimepiride liposomes were prepared by ethanol injection method using varying concentration of cholesterol and lecithin. Drug excipientcompatibility study was performed by FT-IR spectral studies and differential scanning calorimetry studies. Liposomes were evaluated for drugencapsulation efficiency, morphological study by optical microscope, SEM and TEM, vesicle size and zeta potential determination, In -vitro drugrelease & kinetic study and stability studies.Results: The formulations fulfilled all official requirements. The drug release was slow and sustained for >12 hrs. The formulations followed zeroorder kinetics. Zeta potential and stability study for 90 days demonstrated that the formulation was stable at 25¬¬¬¬oC than when refrigerated.Conclusion: Glimepiride was formulated as liposomal formulation after checking the compatibility by DSC and FT-IR studies. The liposomespreparation FA3 was optimized based on the particle size, zeta potential, entrapment efficiency, and drug release characteristics.Keywords: Liposomes, Antidiabetic, Glimepiride, Ethanol-injection method

CRIPTO and its signaling partner GRP78 drive the metastatic phenotype in human osteotropic prostate cancer

CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDHhigh sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDHlow. Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDHhigh sub-population. Additionally, CRIPTO or GRP78 knockdown decreases proliferation, migration, clonogenicity and the size of the metastasis-initiating ALDHhigh sub-population. CRIPTO knockdown reduces the invasion of PC-3M-Pro4Luc2 cells in zebrafish and inhibits bone metastasis in a preclinical mouse model. These results highlight a functional role for CRIPTO and GRP78 in PCa metastasis and suggest that targeting CRIPTO/GRP78 signaling may have significant therapeutic potential.Oncogene advance online publication, 10 April 2017; doi:10.1038/onc.2017.87

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Not AvailableRice grows mostly in tropical and subtropical regions, but it’s very sensitive to higher temperature during reproductive stage especially flowering anthesis. It is necessary to identify genetic donors for heat stress from high temperature rice growing environments. Temperature stress effects at reproductive stage by adopting three different planting dates with 15 days interval each in Environment-1 (e1), Environment-2 (e2) and Environment-3 (E3) with forty-three rice genotypes was studied. The temperature regimes were 35.60C (E1) to 39.2 (E3) at reproductive stage. From the results of AMMI analysis, the environment (E2) was found to be ideal for better identification of genotypes for heat tolerance with desirable traits. The elevated temperature at the time of flowering and maturity determines the yield per se of the genotypes. The hybrids adapted better than parental lines, showing the buffering nature and heterosis for stress tolerance. Under high temperature stress, the response of genotypes depended on developmental stage, but highest sensitivity was recorded at reproductive stage. The time of sowing, days to flowering (duration group), heat escape (early morning flowering) and inbuilt tolerance were the crucial factors in determining the performance of genotypes to varying temperature. Hence, it is necessary to select genotypes by keeping in view the above factors for different temperature stress within and across the environment.Not Availabl