Nurettin Sahiner

Creation of a Drug-Coated Glaucoma Drainage Device Using Polymer Technology: In Vitro and In Vivo Studies

OBJECTIVEnTo create and test a slow-release antifibrotic drug-coated glaucoma drainage device using in vitro and in vivo experiments.nnnMETHODSnA 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.nnnRESULTSnThe 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.nnnCONCLUSIONnOur slow-release drug-coated glaucoma drainage device decreased fibrosis and inflammation in the resulting bleb in a rabbit model.nnnCLINICAL RELEVANCEnThis device could reduce the failure rate of glaucoma drainage devices.

Highly Porous Acrylonitrile-Based Submicron Particles for UO22+ Absorption in an Immunosensor Assay

Our laboratory has previously reported an antibody-based assay for hexavalent uranium (UO(2)(2+)) 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 UO(2)(2+) from spiked groundwater samples.

Inhibition of cell proliferation by mitomycin C incorporated into P(HEMA) hydrogels.

ObjectivesThe technique of mitomycin C (MMC) drug delivery and its application in glaucoma surgery are not standardized with resultant inconsistencies in the results. Also, one time application of MMC does not seem to have the same efficacy after glaucoma drainage device surgeries compared with trabeculectomies. This preliminary study examined the efficacy of a slow release form of MMC for its ability to inhibit cell proliferation in vitro. MethodsMMC was incorporated into 1% P(HEMA) hydrogels using a redox polymerization method. For some experiments, unreacted low molecular weight components were removed from the hydrogels before the MMC was incorporated. Sterile disks (8u2009mm) of each polymer sample were affixed to 60u2009mm tissue culture dishes, and the dishes were inoculated with COS-1 cells or early passage human conjunctival fibroblasts. After 7 days in culture, the number of cells in each dish was determined. Cell morphology was assessed in replicate cultures after fixation and staining. ResultsHydrogels with unreacted low molecular weight components slowed cell proliferation and induced morphologic changes. Early passage human conjunctival fibroblasts were more sensitive than COS-1 cells both to intrinsic contaminants in the hydrogels and to incorporated MMC. Once contaminants had been removed, MMC-loaded hydrogels inhibited conjunctival fibroblast proliferation in a dose-dependent fashion, with an IC50 of ∼0.15u2009mg/g polymer. ConclusionsThis study demonstrates that a slow release form of MMC can inhibit cell proliferation in vitro. Future experiments will focus upon the efficacy of this polymer-bound form during in vivo wound healing.

One step preparation of polymeric maltitol particles, from a sugar molecule, maltitol for biomedical applications

Here, a facile method for the preparation of polymeric particles from a sugar molecule, maltitol (ML) in single step was reported via microemulsion polymerization/crosslinking technique with a high yield, 89u202f±u202f6%. Furthermore, poly(Maltitol) (p(ML)) particles were chemically modified to induce different physicochemical characteristic using different anionic and cationic modifying agents such as taurine (TA) and diethylenetriamine (DETA) to prepare m-p(ML)/TA and m-p(ML)/DETA. The blood compatibility of the p(ML) particles and their modified forms were tested with fresh blood, and found that p(ML) and m-(ML)/DETA particles are blood compatible with about 5% hemolysis, and above 80% blood clotting indices. Moreover, the cytotoxicity results against L929 fibroblast cell line revealed that p(ML) based particle are biocompatible up to 100u202fμg/mL with 85% cell viability regardless of their nature, and at 200u202fμg/mL dosage of p(ML), m-p(ML)/TA and m-p(ML)/DETA particles, the cell viabilities were determined as 83.33, 64.03 and 73.89% on for L929 fibroblast cells implying the slightly less biocompatibility nature of m-p(ML)/TA in accord with the blood compatibility results. Additionally, the apoptotic and necrotic indices were determination for p(ML) based particles on L929 fibroblast cells, and the results revealed that these particles do not induce any and stress on the cells. Also, it does not have genotoxic effect as determined against CHO cells.

Polydopamine particles as nontoxic, blood compatible, antioxidant and drug delivery materials

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 100u2009nm, 18.05 m2/g specific surface area, and mesoporous structure (7.19u2009nm 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 37.5u2009°C. These degradation studies revealed that p(DA) is slightly degradable at pH 1 and pH 7.4 with weight losses of 13.01u2009±u20090.08% and 7.26u2009±u20090.23% 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 21.42u2009±u20090.88%. Furthermore, p(DA) particles were tested for cell toxicity against COS-1 cells and found non-toxic up to 50u2009μg/mL with 95.6u2009±u20094.5% cell viability as compared to 37.5u2009±u20090.03% for DA molecules. The p(DA) particles and DA were also compared for their ability to inhibit α-glucosidase; both inhibited α-glucosidase inhibition activity a concentration-dependent fashion: at concentrations of 500-4000u2009μg/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 1.87u2009±u20090.97% hemolysis ratio up to 50u2009μg/mL concentration and with 86.7% blood clotting index. Interestingly, p(DA) particle can be considered as an effective antioxidant with 33.5u2009±u20093.9u2009μg/ mL total phenol content in terms of gallic acid equivalency and 0.89u2009±u20090. 30u2009μmol/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.