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Application of Supermacroporous Monolithic Hydrophobic Cryogel in Capturing of Albumin

Supermacroporous poly{2-hydroxyethyl methacrylate-co-[N,N-bis(2,6-diisopropylphenyl)-perylene-3,4,9,10-tetracarboxylic diimide]} [poly(HEMA-co-DIPPER)] monolithic cryogel column was prepared by radical cryocopolymerization of HEMA with DIPPER as functional comonomer and N,N′-methylene-bisacrylamide (MBAAm) as crosslinker directly in a plastic syringe for adsorption of albumin. The monolithic cryogel contained a continuous polymeric matrix having interconnected pores of 10–50xa0μm size. Poly(HEMA-co-DIPPER) cryogel was characterized by swelling studies, FTIR, scanning electron microscopy, and elemental analysis. The equilibrium swelling degree of the poly(HEMA-co-DIPPER) cryogel was 14.7xa0g H2O/g dry cryogel. Poly(HEMA-co-DIPPER) cryogel was used in the adsorption/desorption of albumin from aqueous solutions. The nonspecific adsorption of albumin onto plain poly(HEMA) cryogel was very low (3.36xa0g/g polymer). The maximum amount of albumin adsorption from aqueous solution in acetate buffer was 40.9xa0mg/g polymer at pH 5.0. It was observed that albumin could be repeatedly adsorbed and desorbed with the poly(HEMA-co-DIPPER) cryogel without significant loss of adsorption capacity.

Synthesis and in vitro evaluation of dioxopyrrolopyrroles as potential low-affinity fluorescent Ca2+ indicators

Three new low-affinity fluorescent Ca 2+ indicators excitable with visible light, namely 3-phenyl-6-(4-(3-carboxymethoxy-4-(N,N-dicarboxymethylamino)phenyl)phenyl)-2,5-dicarboxymethyl-1,4- dihydropyrrolo(3,4-c)pyrrole-1,4-dione (DPP1), 3-phenyl-6-(5-(3-carboxymethoxy-4-(N,N-dicarboxymethyl- amino)phenyl)thien-2-yl)-2,5-dicarboxymethyl-1,4-dihydropyrrolo(3,4-c)pyrrole-1,4-dione (DPP2) and 3- (thien-2-yl)-6-(5-(3-carboxymethoxy-4-(N,N-dicarboxymethylamino)phenyl)thien-2-yl)-2,5-dicarboxymethyl- 1,4-dihydropyrrolo(3,4-c)pyrrole-1,4-dione (DPP3) have been synthesized and evaluated for their Ca 2+ binding properties via fluorimetric titrations. The in vitro dissociation constant Kd measured at 21 ◦ C in 100 mM KCl buffered solution, pH 7.05, for the Ca 2+ -DPP1 complex is 10 µM; for Ca 2+ -DPP2 and Ca 2+ -DPP3 a Kd value of 20 µM is found. All three indicators form 1 : 1 complexes with Ca 2+ . The fluorescence quantum yields of the uncomplexed forms of DPP1, DPP2 and DPP3 are 1.2 × 10 −2 ,3 .4 × 10 −2 and 3.6 × 10 −2 , respectively. After binding to Ca 2+ these values increase to 4.8 × 10 −2 ,5 .0 × 10 −2 and 5.1 × 10−2, respectively.

Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with 131I

The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with (131)I ((131)I-APH and (131)I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with (131)I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of (131)I-APH and (131)I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as (125)I, (123)I and (124)I as imaging and therapeutic agents in nuclear medical applications.

Synthesis and biodistribution of novel magnetic-poly(HEMA–APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA–APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA–APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90xa0%. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA–APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24xa0h and experimental lipophilicity was determined as 0.12xa0±xa00.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA–APH) labeled with 131I [131I-mag-poly(HEMA–APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA–APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this molecule is applied to adenocarcinoma cell models and tumor-bearing animals.

Radiolabeling of new generation magnetic poly(HEMA–MAPA) nanoparticles with 131I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats

In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with (131) I [(131) I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of (131) I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that (131) I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of (131) I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for (131) I-mag-poly(HEMA-MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for (131) I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and (131) I-mag-poly(HEMA-MAPA) were 0.12u2009±u20090.01 and 1.79u2009±u20090.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440u2009min. It was found that (131) I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60u2009min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important (131) I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results.

Poly(HEMA-co-NBMI) Monolithic Cryogel Columns for IgG Adsorption

Supermacroporous poly(2-hydroxyethyl methacrylate-co-1,5-naphthalene bismaleimide) [poly(HEMA-co-NBMI)] monolithic cryogel column was prepared by free radical cryo-copolymerization of HEMA with NBMI as a hydrophobic functional comonomer and N,N′-methylene-bisacrylamide as cross-linker directly in a plastic syringe for adsorption of albumin. The monolithic cryogel contained a continuous polymeric matrix which has interconnected pores of 10–100xa0μm size. Poly(HEMA-co-NBMI) cryogel was characterized by swelling studies, FTIR and scanning electron microscopy. The equilibrium swelling degree of the poly(HEMA-co-NBMI) cryogel was 10.5xa0g of H2O/g dry cryogel. Poly(HEMA-co-NBMI) cryogel was used in the adsorption/desorption of IgG from aqueous solutions. The maximum amount of IgG adsorption from aqueous solution in phosphate buffer was 98.20xa0mg/g polymer at pHxa07.0. The nonspecific adsorption of IgG onto plain poly(HEMA) cryogel was very low (2.79xa0g/g polymer). It was observed that IgG could be repeatedly adsorbed and desorbed with the poly(HEMA-co-NBMI) cryogel without significant loss of adsorption capacity.