Mehtap Sahiner

Biocompatible and biodegradable poly(Tannic Acid) hydrogel with antimicrobial and antioxidant properties

A novel resourceful bulk poly(Tannic Acid) (p(TA)) hydrogel was prepared by crosslinking TA molecules with an epoxy crosslinker, trimethylolpropane triglycidyl ether (TMPGDE), in an autoclave at 90°C for 2h. The obtained p(TA) hydrogels were in disk form and have highly porous morphology. The swelling characteristics of p(TA) hydrogels were investigated in wound healing pH conditions of pH 5.4, 7.4, and 9 at 37.5°C, and the hydrogels showed good swelling and moisture content behavior. Especially, p(TA) hydrogels were found to be sensitive to pH 9 with 1669% maximum swelling. P(TA) hydrogels were completely degraded at pH 9 hydrolytically in 9 days. Total phenol contents and the effects of scavenging ABTS(+) radicals of degraded p(TA) hydrogels at pH 5.4, 7.4, and 9 were evaluated and calculated in terms of gallic acid equivalent and trolox equivalent antioxidant capacity, respectively, and found to be very effective. Moreover, degraded p(TA) hydrogels display strong antimicrobial behavior against gram positive Staphylococcus aureus, Bacillus subtilis, gram negative Pseudomonas aeruginosa bacteria strains and Candida albicans fungus strain. The WST-1 results indicated that bulk p(TA) hydrogels have no cyctotoxicity to the L929 fibroblast cell line in vitro.

Synthesis, characterization and modification of Gum Arabic microgels for hemocompatibility and antimicrobial studies.

Gum Arabic (GA) microgels were successfully prepared via reverse micellization method with high yield (78.5±5.0%) in 5-100μm size range using divinyl sulfone (DVS) as a crosslinker. The GA microgels were degraded hydrolytically 22.8±3.5% at pH 1 in 20days, whereas no degradation was observed at pH 7.4 and pH 9 at 37°C. By using diethylenetriamine (DETA), and taurine (TA) as chemical modifying agents, GA microgels were chemically modified as GA-DETA and GA-TA, and the zeta potential values of 5.2±4.1 and -24.8±1.3mV were measured, respectively in comparison to -27.3±4.2mV for GA. Moreover, blood compatibility of GA, GA-TA, and GA-DETA microgels was tested via in vitro protein adsorption, % hemolysis ratio, and blood clotting index. All the microgels were hemocompatible with% hemolysis ratio between 0.23 to 2.05, and the GA microgels were found to be highly compatible with a blood clotting index of 81±40. The biocompatibility of GA, GA-DETA and GA-Taurine microgels against L929 fibroblast cells also revealed 84.4, 89.1, and 67.0% cell viability, respectively, at 25.0μg/mL concentration, suggesting great potential in vivo biomedical applications up to this concentration. In addition, 5 and 10mg/mL minimum inhibition concentrations of protonated GA-DETA microgels (GA-DETA-HCl) were determined against E. coli and S. aureus, respectively.

Collagen-based hydrogel films as drug-delivery devices with antimicrobial properties

Collagen (coll)-containing hydrogel films were prepared by mixing degraded collagen with monomers such as acrylamide (AAm), and 2-hydroxy ethylmethacrylate (HEMA) before the polymerization/cross-linking of composites as p(coll-co-AAm), and p(coll-co-HEMA), respectively. These materials were used as drug-delivery devices for potential wound dressing materials by loading and releasing of model drugs such as gallic acid (GA) and naproxen (NP). A linear release profile was obtained up to 32-h release from GA-loaded p(coll-co-AAm) interpenetrating polymeric networks films, and 36-h linear release profile of NP for p(coll-co-HEMA). Furthermore, metal nanoparticles such as Ag and Cu prepared within these hydrogel films offered antimicrobial characteristic against known common bacteria such as Escherichia coli, Bacillus subtilis, and Staphylococcus aureus.

Polyethyleneimine modified poly(Hyaluronic acid) particles with controllable antimicrobial and anticancer effects

Poly(hyaluronic acid) (p(HA)) particles with sizes from few hundred nm to few tens of micrometer were synthesized by using epoxy groups containing crosslinker glycerol diglycidyl ether (GDE) with high yield, 94±5%. P(HA) particles were oxidized by treatment with sodium periodate and then reacted with cationic polyethyleneimine (PEI) at 1:0.5, 1:1, and 1:2 wt ratio of p(HA):PEI to obtain p(HA)-PEI particles. From zeta potential measurements, isoelectronic points of bare p(HA) particles increased to pH 8.7 from 2.7 after modification with cationic PEI. New properties, such as antibacterial property, were attained for p(HA)-PEI after modification. The highest minimum bactericidal concentration (MBC) values were 0.5, 1, and 0.5mg/mL against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis species for 1:0.5 ratio of p(HA)-PEI at 72h incubation time. Moreover, the p(HA)-PEI particles were found to be biocompatible with L929 fibroblast cells, and interestingly, p(HA)-PEI particles were found to inhibit MDA-MB-231 breast and H1299 cancer cell growth depending on amount of PEI in p(HA)-PEI particles.

P(TA) macro-, micro-, nanoparticle-embedded super porous p(HEMA) cryogels as wound dressing material

Super porous poly(2-hydroxy ethyl methacrylate) (p(HEMA)) cryogel was successfully synthesized by using polyethylene glycol diacrylate (p(EGDA)) crosslinker under cryogenic conditions. Poly(Tannic acid) (p(TA)) macro-, micro-, and nanoparticles prepared from a natural polyphenol, tannic acid (TA), were embedded into p(HEMA) cryogel networks to obtain composite p(TA) particle-embedded p(HEMA) cryogel. Different size ranges of spherical p(TA) particles, 2000-500μm, 500-200μm, 200-20μm, and 20-0.5μm size, were included in the cryogel network and illustrated by digital camera, optic microscope, and SEM images of the microgel-cryogel network. The swelling properties and moisture content of p(TA) microgel-embedded p(HEMA) cryogel were investigated at wound healing pH conditions such as pH5.4, 7.4, and 9 at 37.5°C, and the highest swelling capacity was found at pH9 with 972±2% swelling in 30s. Higher amounts of DI water were quickly absorbed by p(HEMA)-based cryogel, and moisture retention within the cryogel structure for a longer time period at room temperature is due to existence of p(TA) particles. Degradation profiles of p(TA) particle-embedded p(HEMA) cryogel were shown to be controlled by different pH conditions, and a linear release profile was found with total cumulative release of 5.8±0.8mg/g TA up to 12days at pH7.4 and 37.5°C. The antioxidant behavior of degraded p(TA) particles from p(HEMA) cryogel were found as 46±1μgmL-1 gallic acid equivalent and 165±18mMtroloxequivalentg-1. The p(TA) particle-embedded p(HEMA) cryogel has high hemocompatibility with 0.0158±0.0126% hemolysis ratio, and effective hemostatic properties with 8.1±0.9 blood clotting index.

Synthesis and characterization of new microgel from tris(2-aminoethyl)amine and glycerol diglycidyl ether as poly(TAEA-co-GDE)

Here, we report a new microgel preparation from tris(2-aminoethyl)amine (TAEA) and glycerol diglycidyl ether (GDE) as p(TAEA-co-GDE) via simple microemulsion polymerization/crosslinking by using L-α lecithin as surfactant and gasoline as organic phase. The p(TAEA-co-GDE) microgels were visualized using optical microscopy and scanning electron microscopy (SEM) with size ranges <10 μm. The prepared particles were found to be positively charged, 23.61 ± 1.2 mV at pH~4.5, according to zeta-potential measurements, and the charge of particles decreased with increase in pH of the medium and become negatively charged after pH 10. The microgel particles were protonated (quaternized) or deprotanated by HCl and NaOH treatments, changing their zeta potential to 33 ± 1.3 mV and 14.53 ± 1.8 mV, respectively. Thermal properties of the prepared particles were observed by TG analysis before and after quaternization, and also after Co(II), Cu(II) and Cd(II) metal ion absorption. Here, we also demonstrated in situ CdS quantum dot (Q-dots) preparation within p(TAEA-co-GDE) microgels. The peak energy of 2.5 eV was observed in the fluorescence spectrum of p(TAEA-co-GDE)-CdS microgel by applying an excitation wavelength of 300 nm. Furthermore, the prepared p(TAEA-co-GDE) particles showed antibacterial characteristics against common bacteria such as Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633 and Pseudomonas aeruginosa ATCC 10145 and have great potential for biomedical use. Additionally, p(TAEA-co-GDE) particles are found to be biocompatible against L929 Fibroblast cells.

Quantitative Clinical Diagnostic Analysis of Acetone in Human Blood by HPLC: A Metabolomic Search for Acetone as Indicator

Using high-performance liquid chromatography (HPLC) and 2,4-dinitrophenylhydrazine (2,4-DNPH) as a derivatizing reagent, an analytical method was developed for the quantitative determination of acetone in human blood. The determination was carried out at 365 nm using an ultraviolet-visible (UV-Vis) diode array detector (DAD). For acetone as its 2,4-dinitrophenylhydrazone derivative, a good separation was achieved with a ThermoAcclaim C18 column (15 cm × 4.6 mm × 3 μm) at retention time (t R) 12.10 min and flowrate of 1 mL min−1 using a (methanol/acetonitrile) water elution gradient. The methodology is simple, rapid, sensitive, and of low cost, exhibits good reproducibility, and allows the analysis of acetone in biological fluids. A calibration curve was obtained for acetone using its standard solutions in acetonitrile. Quantitative analysis of acetone in human blood was successfully carried out using this calibration graph. The applied method was validated in parameters of linearity, limit of detection and quantification, accuracy, and precision. We also present acetone as a useful tool for the HPLC-based metabolomic investigation of endogenous metabolism and quantitative clinical diagnostic analysis.