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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 °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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Few hundred micrometer size microgel capsules from natural locust bean gum (LBG) was synthesized by means of divinyl sulfone (DVS) crosslinking in a surfactant free cyclohexane medium with 100% yield in 1 h. These LBG microgel capsules were chemically modified with different numbers of linear amine containing modifying agents such as ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetraamine (TETA) and branched polyethyleneimine (PEI) to induce cationic character for LBG microgels. The biggest change in zeta potential of LBG microgels that is +44.9 mV from -17.67 mV was observed upon the modification of LBG microgels with branched PEI (LBG/PEI). The blood compatibility studies were revealed that bare LBG microgels possess a good blood compatibility with non-hemolytic value, 0.96 ± 0.15%, and high blood clotting index, 87.35 ± 4.10%, whereas the blood compatibility of LBG/PEI microgels was found to be slightly-hemolytic, 4.96 ± 1.03%, and also moderate blood clotting index, 65.98 ± 98%. Additionally, sodium diclofenac (SDC) as a model drug was loaded into the LBG based microgels by directly loading from solution (absorption) and by chemical conjugation methods for in vitro release studies at physiological conditions, pH 7.4 at 37.5 °C A longer, and sustainable drug release profiles were obtained from chemical drug conjugated LBG microgels and the amine modified LBG microgels., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)