Drug Development and Industrial Pharmacy, Feb 20, 2012
The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certai... more The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells. In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined. NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays. NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs. The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.
Introduction: Low vitamin D (vitD) status has been linked to increased cardiovascular (CV) risk, ... more Introduction: Low vitamin D (vitD) status has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation on CV disease and its determinants, such as lipid metabolism, are not entirely clarified. Hypothesis: We hypothesized that vitD may modulate lipoprotein functions, such as the HDL cholesterol efflux capacity (CEC), which is inversely correlated to CV risk, and the pro-atherogenic serum cholesterol loading capacity (CLC). We evaluated the impact of vitD status normalization on HDL CEC, serum CLC, adipokine profile and subclinical atherosclerosis in premenopausal women. Methods: Healthy premenopausal women with vitD deficiency (n=31) were scheduled for vitD replacement. HDL CEC was measured by a radioisotopic assay and serum CLC by cholesterol fluorimetric quantification in macrophages. Serum adipokines were measured by ELISA. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI), measured with stan...
Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its... more Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its pathogenesis has not been elucidated clearly. Hypothesis: In this study, we aimed to investigate th...
Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs h... more Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs have recently attracted attention for their function as a regulator of immune cell recruitment and function in addition to their tumour-promoting roles. In this study, we aimed to determine the role of CAFs on monocyte recruitment and macrophage polarization in breast cancer. CAFs, which were α-SMA expressing fibroblasts in contrast to normal fibroblasts (NFs), effectively recruited monocytes. Recruitment of monocytes by CAFs might be mediated by monocyte chemotactic protein-1 (MCP-1) as well as stromal cell-derived factor-1 (SDF-1) cytokines. CAFs differentiated the recruited monocytes into M2-like macrophages which are capable of exerting their immunosuppressive roles via the PD-1 axis. CAF-educated monocytes exhibited strong immune suppression unlike NF-educated monocytes and enhanced the motility/invasion of breast cancer cells in addition to increasing the expressions of epithelial–m...
Drug Development and Industrial Pharmacy, Feb 20, 2012
The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certai... more The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells. In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined. NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays. NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs. The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.
Introduction: Low vitamin D (vitD) status has been linked to increased cardiovascular (CV) risk, ... more Introduction: Low vitamin D (vitD) status has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation on CV disease and its determinants, such as lipid metabolism, are not entirely clarified. Hypothesis: We hypothesized that vitD may modulate lipoprotein functions, such as the HDL cholesterol efflux capacity (CEC), which is inversely correlated to CV risk, and the pro-atherogenic serum cholesterol loading capacity (CLC). We evaluated the impact of vitD status normalization on HDL CEC, serum CLC, adipokine profile and subclinical atherosclerosis in premenopausal women. Methods: Healthy premenopausal women with vitD deficiency (n=31) were scheduled for vitD replacement. HDL CEC was measured by a radioisotopic assay and serum CLC by cholesterol fluorimetric quantification in macrophages. Serum adipokines were measured by ELISA. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI), measured with stan...
Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its... more Introduction: Degenerative aortic valve disease is the most prevalent valvular heart disease. Its pathogenesis has not been elucidated clearly. Hypothesis: In this study, we aimed to investigate th...
Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs h... more Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs have recently attracted attention for their function as a regulator of immune cell recruitment and function in addition to their tumour-promoting roles. In this study, we aimed to determine the role of CAFs on monocyte recruitment and macrophage polarization in breast cancer. CAFs, which were α-SMA expressing fibroblasts in contrast to normal fibroblasts (NFs), effectively recruited monocytes. Recruitment of monocytes by CAFs might be mediated by monocyte chemotactic protein-1 (MCP-1) as well as stromal cell-derived factor-1 (SDF-1) cytokines. CAFs differentiated the recruited monocytes into M2-like macrophages which are capable of exerting their immunosuppressive roles via the PD-1 axis. CAF-educated monocytes exhibited strong immune suppression unlike NF-educated monocytes and enhanced the motility/invasion of breast cancer cells in addition to increasing the expressions of epithelial–m...
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