Selin Sagbas

Single step natural poly(tannic acid) particle preparation as multitalented biomaterial.

In this study, we report the preparation of poly(tannic acid) (p(TA)) particles by crosslinking with glycerol diglycidyl ether (GDE) and trimethylolpropane triglycidyl ether (TMPGDE). The p(TA) particles are negatively charged as obtained by the zeta potential measurements, -27mV. P(TA) particles are found to be an effective antioxidant material as 170mgL(-1) of p(TA) particle demonstrated the antioxidant equivalency of 82.5±7.2mgL(-1) of gallic acid (GA), used as standard in Folin-Ciocalteau (FC) method. Additionally, TA and p(TA) particles have a strong antimicrobial effect against Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, and Bacillus subtilis ATCC 6633. Furthermore, p(TA) particles were used as drug delivery materials by using model drugs such as TA itself, and GA in the release studies in PBS at pH7.4 at 37.5°C, and found that p(TA) particles can release 80.8 and 87.4% of the loaded TA and GA, respectively. Interestingly, p(TA) maintained its fluorescent property upon crosslinking of TA units. It is further demonstrated that p(TA) particles are as effective as cisplatin (a cancer drug) against A549 cancerous cells that both showed about 36 and 34% cell viability, respectively whereas linear TA showed 66% cell viability at 37.5μgmL(-1) concentration. Above this concentration p(TA) and cisplatin showed almost the same toxicity against A549 cancerous cells. Additionally, p(TA) particles are found to be much more biocompatible against L929 Fibroblast cells, about 84% cell viability in comparison to linear TA with about 53% at 75μgmL(-1) concentration.

Very fast catalytic reduction of 4-nitrophenol, methylene blue and eosin Y in natural waters using green chemistry: p(tannic acid)–Cu ionic liquid composites

Using tannic acid (TA) as a biopolymer, poly(tannic Acid) (p(TA)) microgels were obtained by cross-linking TA with trimethylolpropane triglycidyl ether (TMPGDE) as cross-linker in a water-in-oil micro emulsion system. Ionic liquid forms of p(TA) micro particles were prepared as Ionic Liquid Colloids (ILC) by post chemical modification of p(TA) particles using quaternization agents such as 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPACl) and ammonia (NH3) in aqueous solution to generate positively-charged ammonium salts on the network. Then the modified p(TA) micro particles were used as template for Co, Ni, and Cu metal nanoparticle preparation in situ after loading of metal salts such as CoCl2, NiCl2, and CuCl2 from ethyl alcohol solution into the p(TA) network, and consequent reduction with sodium borohydride (NaBH4). The prepared metal nanoparticle-containing ILCs of p(TA) microgel composites were used as catalysts in the reduction of toxic organic compounds such as 4-nitrophenol (4-NP), eosin Y (EY), and methylene blue (MB). Various parameters affecting the 4-NP and MB reduction were investigated. The activation energy, enthalpy, and entropy for the reduction of 4-NP to 4-AP catalyzed by ILC p(TA)-co composite catalyst system were calculated as 26.19 kJ mol−1, 23.12 kJ mol−1, and −182.35 J mol−1 K−1, respectively.

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.

Poly(sucrose) micro particles preparation and their use as biomaterials.

Crosslinked p(sucrose) micro particles were synthesized for the first time from sucrose in water-in-oil microemulsion. Using divinyl sulfone (DVS) as crosslinker via reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) p(sucrose) micro particles formed in a single step with very high yield (>90%). The particles have wide size distributions, and negative zeta potential, -27.30 mV, and can be made magnetic field responsive. P(sucrose) particles were shown to be degradable at pHs of 2.5 and 11. Dopamine and gallic acid were used as model drugs for absorption/release studies from p(sucrose) particles. Interestingly, it was shown that p(sucrose) microparticles can be a nutrient for Escherichia coli, and maybe used as a growth medium for other cells, bacteria and organisms. Additionally, the cytotoxic effect of p(sucrose) particles were determined as 26 and 32.5% dead cells against MDA MB-231 cancerous cells and L929 fibroblast cells at 100 ug/ml concentration, respectively. P(sucrose) particles can be safely used for in vivo applications.

Inherently antioxidant and antimicrobial tannic acid release from poly(tannic acid) nanoparticles with controllable degradability

From a natural polyphenol, Tannic acid (TA), poly(TA) nanoparticles were readily prepared using a single step approach with three different biocompatible crosslinkers; trimethylolpropane triglycidyl ether (TMPGDE), poly(ethylene glycol) diglycidyl ether (PEGGE), and trisodium trimetaphosphate (STMP). P(TA) particles were obtained with controllable diameters between 400 to 800nm with -25mV surface charge. The effect of synthesis conditions, such as the emulsion medium, pH values of TA solution, and the type of crosslinker, on the shape, size, dispersity, yield, and degradability of poly(Tannic Acid) (p(TA)) nanoparticles was systematically investigated. The hydrolytic degradation amount in physiological pH conditions of 5.4, 7.4, and 9.0 at 37.5°C were found to be in the order TMPGDE<PEGGE<STMP. Furthermore, the degradation amounts of TA from p(TA) nanoparticles can be controlled by the appropriate choice of crosslinker, and the pH of releasing media. The highest TA release, 600mg/g, was obtained for TMPGDE-crosslinked p(TA) particles in intestinal pH conditions (pH 9) over 3 days; whereas, a slow and linear TA release profile over almost 30 days was obtained by using PEGGE-crosslinked p(TA) in body fluid pH conditions (pH 7.4). The total phenol content of p(TA) particles was calculated as 70±1μgmL(-1) for 170μgmL(-1) p(TA), and the trolox equivalent antioxidant capacity was found to be 2027±104mM trolox equivalent g(-1). Moreover, p(TA) nanoparticles demonstrated strong antimicrobial effects against common bacterial strains. More interestingly, with a higher concentration of p(TA) particles, higher blood clotting indices were obtained.

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.

Multifunctional tunable p(inulin) microgels

Inulin, inulin-silica and modified inulin microgels were prepared in a single step via crosslinking within microemulsion, and used as drug delivery devices. Inulin-silica composite micro particles were also synthesized in the presence of tetraethyl orthosilicate (TEOS) via a water-in-oil microemulsion polymerization/crosslinking technique. To generate porous inulin particles, inulin-silica particles were treated with 0.5M NaOH solution to dissolve silica particles. Furthermore, virgin inulin (p(inulin)) and porous inulin microgels (por-p(inulin)) were quaternized successfully by treatment with 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTMAC) in aqueous solution, generating positive charges on the biopolymer as q-p(inulin). Rosmarinic acid (RA) was used as model drug for loading and release studies by synthesized inulin-based microgels in phosphate buffer solution (PBS) at pH7.4. It was shown that the absorption and release rate are influenced by zeta potential and porosity of the microgels.

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 100 nm, 18.05 m2/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 °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 μg/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 α-glucosidase; both inhibited α-glucosidase inhibition activity a concentration-dependent fashion: at concentrations of 500-4000 μg/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 μg/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 μg/ mL total phenol content in terms of gallic acid equivalency and 0.89 ± 0. 30 μmol/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.