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    Development of Anti-VEGF Prolonged Release Drug Delivery System Containing PLL Dendrimer and Hyaluronic Acid
    (Maik Nauka/Interperiodica/Springer, 2022) Gedik, G.; Oztabag, C. K.; Sarp, O.; Nazli, H.; Tiranbesli, G.; Kurt, A. H.; Dinc, E.
    In this study we aimed to develop anti-vascular endothelial growth factors (anti-VEGF) drug delivery systems that long-term sustained release using dendrimer technology and to evaluate its possible cytotoxic effects on the retina pigment epithelial cells (ARPE-19) and the irritation potential by Hen's Egg Test on a chorioallantoic membrane (HET-CAM) analysis. The drug carrier gel formulation was prepared by adding hyaluronic acid (HA) after bevacizumab (BEV) was complexed with poly-L-lysine (PLL) dendrimer. The formulations were determined by the particle size, polydispersity index (PDI) values, zeta potential, pH, optical clarity, and their content. The UV- spectrophotometric analytical methods were developed, validated and applied for the kinetic studies. Prolonged BEV release from formulations has been observed for up to 21 days. Cell viability was evaluated with the XTT assay. VEGF and BEV levels in the medium were measured using a human VEGF and BEV ELISA kit, respectively. HET-CAM assays were conducted to determine the irritation potential. The clarity of gel formulation was found to be clear and satisfactory (double +). The pH of gel formulation ranged between 6.39 and 6.95. The zeta potential of formulations ranged between +3.9 and -1.5 mV. The particle size of formulations ranged between 15 and 302 nm. The loading efficiency (LE) of the complex formulation was found 79.04%. The formulation's kinetic behavior was determined by the Higuchi and Korsmeyer-Peppas model. The formulations did not cause any irritation. According to the results obtained, gel formulation was innovative, effective and suitable for treatment. However, animal experiments and clinical studies should also be performed.
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    Effects of intravitreal injection of bevacizumab on nitric oxide levels
    (Nature Publishing Group, 2015) Dinc, E.; Yildirim, O.; Ayaz, L.; Ozcan, T.; Yilmaz, S. N.
    Purpose This study aimed to determine the possible effects of single-dose intravitreal bevacizumab on nitric oxide (NO) levels in serum and remote organs and to reveal one of the possible mechanisms in the pathophysiology of hypertension. Methods Thirty-eight adult New Zealand albino rabbits were divided into a control group (no injection was performed, killed on day 28 of the study), group 1 (killed on day 1 of the study), group 2 (killed on day 7 of the study), group 3 (killed on day 14 of the study), and group 4 (killed on day 28 of the study). The right eyes of the animals in groups 1-4 received an intravitreal single injection of 1.25mg (0.05ml) bevacizumab (Avastin), and their brain, heart, liver, kidney, and blood samples were collected. NO levels were evaluated in the serum and organ homogenates. Kidney tissues were assessed by electron microscopy. Results Serum, brain, kidney, and liver NO levels significantly decreased in groups 2, 3, and 4 as compared with the control group (P<0.05). In addition, heart NO levels significantly decreased in groups 3 and 4 compared with the control group (P<0.05). There were no electron microscopic changes in the kidneys of either group. Conclusions This study demonstrated that single intravitreal injection of bevacizumab decreased NO levels in serum, brain, heart, liver, and kidneys. In addition, there were no electron microscopic changes in the kidneys.