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Öğe Antimicrobial activity and biocompatibility of slow-release hyaluronic acid-antibiotic conjugated particles(Elsevier, 2020) Zhang, Ze; Sağbaş Suner, Selin; Blake, Diane A.; Ayyala, Ramesh S.; Şahiner, NurettinHere, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2 weeks. Slow degradable HA particles were obtained with 35.2 wt% degradation within 21 days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C + A processes) from 148 +/- 8 to 355 +/- 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 +/- 7.35 and 25.00 +/- 0.68 mg/g, respectively, from drug-conjugated HA particles in 100 h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1 h to 1 week. The MBC values were measured as 0.25, 4.0, and 0.25 mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72 h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5 days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.Öğe Arsenic (V) removal with modifiable bulk and nano p(4-vinylpyridine)-based hydrogels: The effect of hydrogel sizes and quarternization agents(Elsevier, 2011) Şahiner, Nurettin; Özay, Özgür; Aktaş, Nahit; Blake, Diane A.; John, Vijay T.Macrogels and nanogels (5 x 6 mm and 370 nm dimensions, respectively) based on 4-vinylpyridine (p-(4VP)) were prepared using redox and microemulsion techniques. The p(4-VP)-based materials were quaternized with HCl/alkyhalides having different chain lengths to tune the charges (macro and nanogels) and size of nanogels. By developing positive charge on the p(4-VP) materials, they behaved as ion exchangers and used in removal of As(V) from aqueous environments. The prepared p(4-VP) materials were also rendered responsive to magnetic field by in situ incorporation of magnetic metal nanoparticles inside macro p(4-VP) hydrogels and by encapsulation of separately prepared magnetic ferrites by nanosized p(4-VP) particles. Nanoparticles quaternized with HCl (p(4-VP)-HCl) (1 g) removed over 95% of As(V) from a stock solution (10 mg L-1 1000 mL) in 15 min whereas bulk hydrogels removed >82% of the As(V) from an equivalent solution in similar to 12 h. Parameters effecting the As(V) removal, including pH, temperature and ionic strength, were also investigated. The synthesized magnetic p(4-VP) composites could be reused after elution with NaOH and regeneration with quaternization agents; these procedures were facilitated using an externally applied magnetic field. The Langmuir and Freundlich adsorption isotherms were also applied to study the removal of As(V) from aqueous environments. (C) 2011 Elsevier B.V. All rights reserved.Öğe COLL 246-Hyaluronic acid hydrogel particles with micron and nano dimensions and their applications in drug delivery(Amer Chemical Soc, 2009) Ilgın, Pınar; Özay, Hava; Aktaş, Nahit; John, Vijay T.; Blake, Diane A.; Ayyala, Ramesh S.; Şahiner, Nurettin[Anstract Not Available]Öğe Creation of a Drug-Coated Glaucoma Drainage Device Using Polymer Technology(Amer Medical Assoc, 2009) Şahiner, Nurettin; Kravitz, Daniel J.; Qadir, Rabah; Blake, Diane A.; Haque, Salima; John, Vijay T.; Margo, Curtis E.Objective: To create and test a slow-release antifibrotic drug-coated glaucoma drainage device using in vitro and in vivo experiments. Methods: A slow-release device incorporating mitomycin C in poly(2-hydroxyethyl methacrylate) disks was developed using redox-polymerization techniques. A standardized preparation of this drug delivery device was attached to the Ahmed glaucoma valve (model FP7; New World Medical, Inc, Rancho Cucamonga, California). Semicircular disks (5 x 6 mm) of P(HEMA)-mitomycin C containing varying concentrations of mitomycin C per gram dry weight of the gel were attached to the lower half of an Ahmed glaucoma valve plate. Water was pumped through the modified Ahmed glaucoma valve at a rate comparable to that of aqueous humor outflow, and mitomycin C release was measured. Modified and unmodified Ahmed glaucoma valves were implanted in a rabbit model, and drug release and fibrosis were assessed after 3 months. Results: The P(HEMA)-mitomycin C device released mitomycin C in vitro over 1 to 2 weeks. Studies in rabbits revealed that mitomycin C was released from the disks during the 3-month implantation. Histologic analysis demonstrated a significant reduction in inflammatory reaction and fibrosis in the resulting blebs. Conclusion: Our slow-release drug-coated glaucoma drainage device decreased fibrosis and inflammation in the resulting bleb in a rabbit model. Clinical Relevance: This device could reduce the failure rate of glaucoma drainage devices.Öğe Enhancement of biocompatibility and carbohydrate absorption control potential of rosmarinic acid through crossinking into microparticles(Elsevier, 2019) Şahiner, Mehtap; Blake, Diane A.; Fullerton, Mitchell L.; Sağbaş Suner, Selin; Sunol, Aydın K.; Şahiner, NurettinRosmarinic acid (RA), a bioflavonoid and antioxidant that exists in plants of the Lamiaceae family, was crosslinked into particles as poly(Rosmarinic Acid) (p(RA)) via an emulsion crosslinking method. The particles were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance C-13 NMR spectroscopy, and thermal gravimetric analysis. The zeta potential values of p(RA) particles were determined at different pHs; the isoelectric point was estimated as pH 1.2. The release of monomeric RA from the particles at 37.5 degrees C was found to be similar at different pHs, 1.0, 7.4, and 11.0. The effects of p(RA) on hemolysis and coagulation were found to be minimal. The antioxidant activity of p(RA) particles and RA monomer were almost indistinguishable suggesting that p(RA) particles may be used as an antioxidant. On a per weight basis, p(RA) particles were similar to 66% less cytotoxic to mammalian cells that RA monomer, as assessed using COS-1 cells. In addition, p(RA) was an 8.6-fold stronger inhibitor of alpha-glycosidase than RA; the IC(50)s of the monomer and particles were 0.121 and 0.014 mg/mL, respectively. The strong inhibitory effect of p(RA) on alpha-glycosidase, coupled with its reduced cytotoxicity and antioxidant activity, provide new opportunities for the use of p(RA). (C) 2019 Elsevier B.V. All rights reserved.Öğe Fabrication of Biodegradable Poly(naringin) Particles with Antioxidant Activity and Low Toxicity(Amer Chemical Soc, 2018) Şahiner, Mehtap; Şahiner, Nurettin; Sağbaş, Selin; Fullerton, Mitchell L.; Blake, Diane A.Naringin (NR, 4', 5,7 trihydrocyflavanone-7-O-rhamnoglucoside) is a flavanone found in citrus fruit that is composed of a phenolic compound, naringenin, and a disaccharide, neohesperidose. Poly(NR) [p(NR)] particles in the size range of few micrometers to few hundred nanometers were prepared from highly purified NR and subsequently characterized using UV/visible spectroscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, thermogravimetric analysis, and zeta potential measurements. The hydrolytic degradation of p(NR) particles at 37.5 degrees C was investigated at pHs 5.4, 7.4, and 9.0. The particles degraded most rapidly at pH 7.4, with >90% degradation after 5 h. The cytotoxicity was assessed by growing COS-1 fibroblasts for 5 days in the presence of increasing concentrations of NR or eluates from the p(NR) particles. Both NR and p(NR) particles were nontoxic for these mammalian fibroblasts; at the highest concentration tested (571 mu g/mL), the percentages of surviving cells after 5 days in culture were 96.7 +/- 0.93 and 91 +/- 11% for NR and p(NR), respectively. The effect of p(NR) on red blood cell hemolysis was also negligible (<2%) at concentrations up to 100 mu g/mL; unpolymerized NR showed slightly higher levels of hemolysis than the p(NR) particles, but values never exceeded 5% at 50 and 100 mu g/mL. Both NR and p(NR) stimulated blood coagulation in a dose-dependent manner; the hemostatic effect was greater for p(NR), which, at 100 mu g/mL, stimulated in vitro blood clotting by similar to 50%. Neither NR nor eluates from p(NR) particles inhibited alpha-glucosidase activity; in fact, both provided a modest (10-30%) stimulation at concentrations from 0.67 to 1.67 mg/mL. p(NR) particles are easily synthesized, break down readily at physiological pH, and have excellent blood and biocompatibility. As such, they will be a useful carrier for drug delivery and as an oral antioxidant supplement.Öğe Highly Porous Acrylonitrile-Based Submicron Particles for UO22+ Absorption in an immunosensor Assay(Amer Chemical Soc, 2012) Şahiner, Nurettin; Yu, Haini; Tan, Grace; He, Jibao; John, Vijay T.; Blake, Diane A.Our laboratory has previously reported an antibody-based assay for hexavalent uranium (UO22+) that could be used on-site to rapidly assess uranium contamination in environmental water samples (Melton, S. J.; et al. Environ. Sci. Technol. 2009, 43, 6703-6709). To extend the utility of this assay to less-characterized sites of uranium contamination, we required a uranium-specific adsorbent that would rapidly remove the uranium from groundwater samples, while leaving the concentrations of other ions in the groundwater relatively unaltered. This study describes the development of hydrogel particles containing amidoxime groups that can rapidly and selectively facilitate the uptake of uranyl ions. A miniemulsion polymerization technique using SDS micelles was employed for the preparation of the hydrogel as linked submicrometer particles. In polymerization, acrylonitrile was used as the initial monomer, ethylene glycol dimethacrylate as the crosslinker and 2-hydroxymethacrylate, 1-vinyl-2-pyrrolidone, acrylic acid, or methacrylic acid were added as co-monomers after the initial seed polymerization of acrylonitrle. The particles were characterized by transmission electron spectroscopy, scanning electron microscopy (SEM) and cryo-SEM. The amidoximated particles were superior to a commercially available resin in their ability to rapidly remove dissolved UO22+ from spiked groundwater samples.Öğe POLY 225-Acrylonitrile-based functional hydrogel particles(Amer Chemical Soc, 2008) Şahiner, Nurettin; Yu, Haini; Tan, Grace; He, Jibao; John, Vijay T.; Blake, Diane A.Öğe Polydopamine particles as nontoxic, blood compatible, antioxidant and drug delivery materials(Elsevier Science Bv, 2018) Şahiner, Nurettin; Sağbaş, Selin; Şahiner, Mehtap; Blake, Diane A.; Reed, Wayne F.Herein, the potential biomedical application of poly(3,4-dihyroxyphenyl)ethylamine, (poly(dopamine)-p(DA)) particles is reported. P(DA) particles with the size about 100 nm, 18.05 m(2)/g specific surface area, and mesoporous structure (7.19 nm pore width) were prepared and shown to be chemically modifiable using chlorosulfonic acid (CSA) and 3-CHloro-2 hydroxypropyl) trimethylammonium chloride solution (CHPACl) to obtain sulfonic acid and quaternary amine group containing modified p(DA) particles, m-p(DA)-CSA and m-p (DA)-CHPACl particles, respectively. The hydrolytic degradation of p(DA) particles at different pHs, including 1, 7.4 and 11, was carried out at 37.5 degrees C. These degradation studies revealed that p(DA) is slightly degradable at pH 1 and pH 7.4 with weight losses of 13.01 +/- 0.08% and 7.26 +/- 0.23% in 11 days, respectively. At pH 11, a sustained degradation that is almost linear degradation with time was observed for up to 30 days, with a total weight loss of 21.42 +/- 0.88%. Furthermore, p(DA) particles were tested for cell toxicity against COS-1 cells and found non-toxic up to 50 mu g/mL with 95.6 +/- 4.5% cell viability as compared to 37.5 +/- 0.03% for DA molecules. The p(DA) particles and DA were also compared for their ability to inhibit alpha-glucosidase; both inhibited alpha-glucosidase inhibition activity a concentration-dependent fashion: at concentrations of 500-4000 mu g/mL, p(DA) provided 8.52-27.67% inhibition while DA inhibited 42.8-67.7% over the same concentration range. Furthermore, p(DA) particles were found to be blood compatible e.g., non-hemolytic with 1.87 +/- 0.97% hemolysis ratio up to 50 mu g/mL concentration and with 86.7% blood clotting index. Interestingly, p(DA) particle can be considered as an effective antioxidant with 33.5 +/- 3.9 mu g/mL total phenol content in terms of gallic acid equivalency and 0.89 +/- 0.30 mu mol/g trolox equivalent antioxidant capacity (TEAC). Finally, p(DA) particles and their modified forms, m-p(DA)-CSA, and m-p(DA)-CHPACl, were shown to be useful as active agent/drug delivery devices by using acyclovir as a model drug that can be readily loaded into particles and released at longer times at higher amounts for the modified p(DA) particles at physiological conditions.
