Polydopamine Coating of Graphitic Carbon Nitride, g-C3N4, Improves Biomedical Application.

Graphitic carbon nitride (g-C3N4) is an intriguing nanomaterial that exhibits photoconductive fluorescence properties under UV-visible light. Dopamine (DA) coating of g-C3N4 prepared from melamine was accomplished via self-polymerization of DA as polydopamine (PDA). The g-C3N4 was coated with PDA 1, 3, and 5 times repeatedly as (PDA@g-C3N4) in tris buffer at pH 8.5. As the number of PDA coatings was increased on g-C3N4, the peak intensity at 1512 cm-1 for N-H bending increased. In addition, the increased weight loss values of PDA@g-C3N4 structures at 600 °C from TGA thermograms confirmed that the coating was accomplished. The band gap of g-C3N4, 2.72 eV, was reduced to 0.87 eV after five coatings with PDA. A pristine g-C3N4 was found to have an isoelectric point (IEP) of 4.0, whereas the isoelectric points of 1PDA@g-C3N4 and 3PDA@g-C3N4 are close to each other at 3.94 and 3.91, respectively. On the other hand, the IEP of 5PDA@g-C3N4 was determined at pH 5.75 assuming complete coating with g-C3N4. The biocompatibility of g-C3N4 and PDA@g-C3N4 against L929 fibroblast cell lines revealed that all PDA@g-C3N4 coatings were found to be biocompatible up to a 1000 mg/mL concentration, establishing that PDA coatings did not adversely affect the biocompatibility of the composite materials. In addition, PDA@g-C3N4 was screened for antioxidant potential via total phenol content (TPC) and total flavonoid content assays and it was found that PDA@g-C3N4 has recognizable TPC values and increased linearly with an increased number of PDA coatings. Furthermore, blood compatibility of pristine g-C3N4 is enhanced considerably upon PDA coating, affirmed by hemolysis and the blood clotting index%. Additionally, α-glucosidase inhibitory properties of PDA@g-C3N4 structures revealed that 67.6 + 9.8% of this enzyme was evenly inhibited by 3PDA@g-C3N4 structure.

Fluorescent Graphitic Carbon Nitride (g-C3N4)-Embedded Hyaluronic Acid Microgel Composites for Bioimaging and Cancer-Cell Targetability as Viable Theragnostic.

Fluorescent graphitic carbon nitride (g-C3N4) doped with various heteroatoms, such as B, P, and S, named Bg-C3N4, Pg-C3N4, and Sg-C3N4, were synthesized with variable band-gap values as diagnostic materials. Furthermore, they were embedded within hyaluronic acid (HA) microgels as g-C3N4@HA microgel composites. The g-C3N4@HA microgels had a 0.5-20 µm size range that is suitable for intravenous administration. Bare g-C3N4 showed excellent fluorescence ability with 360 nm excitation wavelength and 410-460 emission wavelengths for possible cell imaging application of g-C3N4@HA microgel composites as diagnostic agents. The g-C3N4@HA-based microgels were non-hemolytic, and no clotting effects on blood cells or cell toxicity on fibroblasts were observed at 1000 µg/mL concentration. In addition, approximately 70% cell viability for SKMEL-30 melanoma cells was seen with Sg-C3N4 and its HA microgel composites. The prepared g-C3N4@HA and Sg-C3N4@HA microgels were used in cell imaging because of their excellent penetration capability for healthy fibroblasts. Furthermore, g-C3N4-based materials did not interact with malignant cells, but their HA microgel composites had significant penetration capability linked to the binding function of HA with the cancerous cells. Flow cytometry analysis revealed that g-C3N4 and g-C3N4@HA microgel composites did not interfere with the viability of healthy fibroblast cells and provided fluorescence imaging without any staining while significantly decreasing the viability of cancerous cells. Overall, heteroatom-doped g-C3N4@HA microgel composites, especially Sg-C3N4@HA microgels, can be safely used as multifunctional theragnostic agents for both diagnostic as well as target and treatment purposes in cancer therapy because of their fluorescent nature.

Cell Staining Microgels Derived from a Natural Phenolic Dye: Hematoxylin Has Intriguing Biomedical Potential.

Hematoxylin (HT) as a natural phenolic dye compound is generally used together with eosin (E) dye as H&E in the histological staining of tissues. Here, we report for the first time the polymeric particle preparation from HT as poly(Hematoxylin) ((p(HT)) microgels via microemulsion method in a one-step using a benign crosslinker, glycerol diglycidyl ether (GDE). P(HT) microgels are about 10 µm and spherical in shape with a zeta potential value of -34.6 ± 2.8 mV and an isoelectric point (IEP) of pH 1.79. Interestingly, fluorescence properties of HT molecules were retained upon microgel formation, e.g., the fluorescence emission intensity of p(HT) at 343 nm was about 2.8 times less than that of the HT molecule at λex: 300 nm. P(HT) microgels are hydrolytically degradable and can be controlled by using an amount of crosslinker, GDE, e.g., about 40%, 20%, and 10% of p(HT) microgels was degraded in 15 days in aqueous environments for the microgels prepared at 100, 200, and 300% mole ratios of GDE to HT, respectively. Interestingly, HT molecules at 1000 mg/mL showed 22.7 + 0.4% cell viability whereas the p(HT) microgels exhibited a cell viability of 94.3 + 7.2% against fibroblast cells. Furthermore, even at 2000 mg/mL concentrations of HT and p(HT), the inhibition% of α-glucosidase enzyme were measured as 93.2 ± 0.3 and 81.3 ± 6.3%, respectively at a 0.03 unit/mL enzyme concentration, establishing some potential application of p(HT) microgels for neurogenerative diseases. Moreover, p(HT) microgels showed two times higher MBC values than HT molecules, e.g., 5.0 versus 2.5 mg/mL MIC values against Gram-negative E. coli and Gram-positive S. aureus, respectively.

B, P, and S heteroatom doped, bio- and hemo-compatible 2D graphitic-carbon nitride (g-C3N4) with antioxidant, light-induced antibacterial, and bioimaging endeavors.

The synthesis of two-dimensional (2D) graphiticg-C3N4and heteroatom-doped graphitic H@g-C3N4(H: B, P, or S) particles were successfully done using melamine as source compounds and boric acid, phosphorous red, and sulfur as doping agents. The band gap values of 2Dg-C3N4, B50@g-C3N4, P50@g-C3N4, and S50@g-C3N4structures were determined as 2.90, 3.03, 2.89, and 2.93 eV, respectively. The fluorescent emission wavelengths of 2Dg-C3N4, B50@g-C3N4, P50@g-C3N4, and S50@g-C3N4structures were observed at 442, 430, 441, and 442 nm, respectively upon excitation atλEx= 325 nm. There is also one additional new emission wavelength was found at 345 nm for B50@g-C3N4structure. The blood compatibility test results ofg-C3N4, B50@g-C3N4, P50@g-C3N4, and S50@g-C3N4structures revealed that all materials are blood compatible with <2% hemolysis and >90% blood clotting indices at 100µg ml-1concentration. The cell toxicity of the prepared 2D graphitic structures were also tested on L929 fibroblast cells, and even the heteroatom doped hasg-C3N4structures induce no cytotoxicity was observed with >91% cell viability even at 250µg ml-1particle concentration with the exception of P50@g-C3N4which as >75 viability. Moreover, for 2Dg-C3N4, B50@g-C3N4, and S50@g-C3N4constructs, even at 500µg ml-1concentration, >90% cell viabilities was monitored. As a diagnostic material, B50@g-C3N4was found to have significantly high penetration and distribution abilities into L929 fibroblast cells granting a great potential in fluorescence imaging and bioimaging applications. Furthermore, the elemental doping with B, P, and S ofg-C3N4were found to significantly increase the photodynamic antibacterial activity e.g. more than half of bacterial elimination by heteroatom-doped forms ofg-C3N4under UVA treatment was achieved.

Rapid Pathogen Purge by Photosensitive Arginine-Riboflavin Carbon Dots without Toxicity.

Photo-activatable antipathogenic carbon dots (CDs) were prepared by carbonization of citric acid and arginine (Arg) via 3 min microwave treatment for use in the eradication of common microorganisms. Nitrogen-doped Arg CDs were spherical in shape with a size range of 0.5 to 5 nm. The Arg CDs were modified with fluorescent dyes, such as fluorescein sodium salt (FSS, as Arg-FSS) and riboflavin (RBF, as Arg-RBF), to improve antimicrobial potency by enhancing their application in photodynamic therapy. The modified Arg CDs afforded fluorescence emission properties at 520 nm in the green region in addition to excellent blue fluorescence intensity at 420 nm under 345 nm excitation upon their FSS and RBF conjugation, respectively. Although the cytotoxicity of Arg CDs was decreased for Arg-RBF CDs to 91.2 ± 0.7% cell viability for fibroblasts, the Arg-based CDs could be safely used for intravenous applications at 1000 µg/mL concentration. The Arg CDs showed broad-spectrum antimicrobial activity against common pathogens and the minimum inhibitory concentration of Arg CDs was almost two-fold decreased for the modified forms without UV light. However, faster and more effective antibacterial activity was determined for photosensitive Arg-RBF CDs, with total bacterial eradication upon UV-A light exposure for 30 min.

Water Dynamics in Dextran-Based Hydrogel Micro/Nanoparticles Studied by NMR Diffusometry and Relaxometry.

Water dynamics in mesoporous dextran hydrogel micro/nanoparticles was investigated by means of nuclear magnetic resonance (NMR) techniques. High-resolution 1H NMR spectra and pulsed field gradient (PFG) NMR diffusometry measurements obtained on swollen state dextran micro/nanogel revealed the existence of different fractions of water molecules based on their interaction with the gel matrix. In addition to the translational diffusion of bulk water, two more diffusion processes characterized with self-diffusion coefficients 1 and 2 orders of magnitude smaller than that of bulk water were identified. 1H spin-lattice relaxation dispersion profiles obtained for a broad range of Larmor frequencies using fast field cycling (FFC) and conventional NMR relaxometry techniques allowed us to further clarify the mechanisms of molecular motion. According to the water proton pool fractions and associated self-diffusion coefficients, it is shown that the relaxation contribution associated with reorientation-mediated translational motions (RMTDs) dominates the relaxation dispersion observed at intermediate frequencies. At very low frequencies, the spin-lattice relaxation rate is dominated by the slow solid-gel dynamics probed by the water molecules interacting with the pores' surface hydroxyl groups due to the rapid chemical exchange between surface hydroxyl groups and free water. The correlation time for the thumbling-like motion of the dextran gel was found to be in the submillisecond range. The values of the self-diffusion and coherence lengths associated with motion of water molecules interacting with the solid-gel particles are consistent with the particle size and pore size distributions obtained for the studied dextran gels.

ESI-IM-MS characterization of cyclodextrin complexes and their chemically cross-linked alpha (α-), beta (ß-) and gamma (γ-) cyclodextrin particles as promising drug delivery materials with improved bioavailability.

Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (ß-) and gamma (γ-) CD particles were prepared by directly using α-, ß-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(ß-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(ß-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, ß-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of ß-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

Carboxymethyl Chitosan Microgels for Sustained Delivery of Vancomycin and Long-Lasting Antibacterial Effects.

Carboxymethyl chitosan (CMCh) is a unique polysaccharide with functional groups that can develop positive and negative charges due to the abundant numbers of amine and carboxylic acid groups. CMCh is widely used in different areas due to its excellent biocompatibility, biodegradability, water solubility, and chelating ability. CMCh microgels were synthesized in a microemulsion environment using divinyl sulfone (DVS) as a crosslinking agent. CMCh microgel with tailored size and zeta potential values were obtained in a single stem by crosslinking CMCh in a water-in-oil environment. The spherical microgel structure is confirmed by SEM analysis. The sizes of CMCh microgels varied from one micrometer to tens of micrometers. The isoelectric point of CMCh microgels was determined as pH 4.4. Biocompatibility of CMCh microgels was verified on L929 fibroblasts with 96.5 ± 1.5% cell viability at 1 mg/mL concentration. The drug-carrying abilities of CMCh microgels were evaluated by loading Vancomycin (Van) antibiotic as a model drug. Furthermore, the antibacterial activity efficiency of Van-loaded CMCh microgels (Van@CMCh) was investigated. The MIC values of the released drug from Van@CMCh microgels were found to be 68.6 and 7.95 µg/mL against E. coli and S. aureus, respectively, at 24 h contact time. Disk diffusion tests confirmed that Van@CMCh microgels, especially for Gram-positive (S. aureus) bacteria, revealed long-lasting inhibitory effects on bacteria growth up to 72 h.

Super-Macroporous Pulluan Cryogels as Controlled Active Delivery Systems with Controlled Degradability.

Here, super-macroporous cryogel from a natural polysaccharide, pullulan was synthesized using a cryo-crosslinking technique with divinyl sulfone (DVS) as a crosslinker. The hydrolytic degradation of the pullulan cryogel in various simulated body fluids (pH 1.0, 7.4, and 9.0 buffer solutions) was evaluated. It was observed that the pullulan cryogel degradation was much faster in the pH 9 buffer solution than the pH 1.0 and 7.4 buffer solutions in the same time period. The weight loss of the pullulan cryogel at pH 9.0 within 28 days was determined as 31% ± 2%. To demonstrate the controllable drug delivery potential of pullulan cryogels via degradation, an antibiotic, ciprofloxacin, was loaded into pullulan cryogels (pullulan-cipro), and the loading amount of drug was calculated as 105.40 ± 2.6 µg/mg. The release of ciprofloxacin from the pullulan-cipro cryogel was investigated in vitro at 37.5 °C in physiological conditions (pH 7.4). The amount of drug released within 24 h was determined as 39.26 ± 3.78 µg/mg, which is equal to 41.38% ± 3.58% of the loaded drug. Only 0.1 mg of pullulan-cipro cryogel was found to inhibit half of the growing Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) colonies for 10 min and totally eradicated within 2 h by the release of the loaded antibiotic. No significant toxicity was determined on L929 fibroblast cells for 0.1 mg drug-loaded pullulan cryogel. In contrast, even 1 mg of drug-loaded pullulan cryogel revealed slight toxicity (e.g., 66% ± 9% cell viability) because of the high concentration of released drug.

Biocompatible Glycol Chitosan Microgels as Effective Drug Carriers.

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels' possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 µg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.

Force-Based Characterization of the Wetting Properties of LDPE Surfaces Treated with CF4 and H2 Plasmas.

Low-density polyethylene (LDPE) films are widely used in packaging, insulation and many other commodity applications due to their excellent mechanical and chemical properties. However, the water-wetting and water-repellant properties of these films are insufficient for certain applications. In this study, bare LDPE and textured LDPE (T-LDPE) films were subjected to low-pressure plasmas, such as carbon tetrafluoride (CF4) and hydrogen (H2), to see the effect of plasma treatment on the wetting properties of LDPE films. In addition, the surface of the LDPE film was textured to improve the hydrophobicity through the lotus effect. The LDPE and T-LDPE films had contact angle (θ) values of 98.6° ± 0.6 and 143.6° ± 1.0, respectively. After CF4 plasma treatments, the θ values of the surfaces increased for both surfaces, albeit within the standard deviation for the T-LDPE film. On the other hand, the contact angle values after H2 plasma treatment decreased for both surfaces. The surface energy measurements supported the changes in the contact angle values: exposure to H2 plasma decreased the contact angle, while exposure to CF4 plasma increased the contact angle. Kinetic friction force measurements of water drops on LDPE and T-LDPE films showed a decrease in friction after the CF4 plasma treatment, consistent with the contact angle and surface energy measurements. Notably, the kinetic friction force measurements proved to be more sensitive compared to the contact angle measurements in differentiating the wetting properties of the T-LDPE versus 3× CF4-plasma-treated LDPE films. Based on Atomic Force Microscopy (AFM) images of the flat LDPE samples, the 3× CF4 plasma treatment did not significantly change the surface morphology or roughness. However, in the case of the T-LDPE samples, Scanning Electron Microscopy (SEM) images showed noticeable morphological changes, which were more significant at sharp edges of the surface structures.

Physically Crosslinked Chondroitin Sulfate (CS)-Metal Ion (M: Fe(III), Gd(III), Zn(II), and Cu(II)) Particles for Versatile Applications and Their Biosafety.

Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS-metal ion-containing particles in the micrometer to a few hundred nanometer size range are injectable materials for intravenous administration. The CS-metal ion-containing particles are safe biomaterials for biological applications because of their perfect blood compatibility and no significant cytotoxicity on L929 fibroblast cells up to a 10 mg/mL concentration. Furthermore, CS-Zn(II) and CS-Cu(II) particles show excellent antibacterial susceptibility, with 2.5-5.0 mg/mL minimum inhibition concentration (MIC) values against Escherichia coli and Staphylococcus aureus. Moreover, the in vitro contrast enhancement abilities of aqueous CS-metal ion particle suspensions in magnetic resonance imaging (MRI) were determined by obtaining T1- and T2-weighted MR images using a 0.5 Tesla MRI scanner and by calculating the water proton relaxivities. Therefore, these CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) particles have significant potential as antibacterial additive materials and MRI contrast enhancement agents with less toxicity.

Physically and Chemically Crosslinked, Tannic Acid Embedded Linear PEI-Based Hydrogels and Cryogels with Natural Antibacterial and Antioxidant Properties.

Linear polyethyleneimine (L-PEI) was obtained from the acidic hydrolysis of poly(2-ethyl-2-oxazoline) and employed in the synthesis of physically crosslinked L-PEI hydrogel, PC-L-PEIH, chemically crosslinked L-PEI hydrogel, CC-L-PEIH, and cryogels, CC-L-PEIC. The preparation of L-PEI-based hydrogel networks was carried out in two ways: 1) by cooling the L-PEI solution from 90 °C to room temperature, and 2) by crosslinking L-PEI chains with a crosslinker, glycerol diglycidyl ether = 20 °C for CC-L-PEIC. Furthermore, a polyphenolic compound, tannic acid (TA), with superior antibacterial, antioxidant, and anti-inflammatory properties as an active biomedical functional agent, was encapsulated during the synthesis process within L-PEI-based hydrogels and cryogels, at 10% and 25% (w/w) based on the L-PEI amount. A linear and higher TA release was observed from physically crosslinked PEI-based hydrogels containing 10% and 25% TA-containing PC-L-PEI/TAH within 6 h, with 9.5 ± 05 mg/g and 60.2 ± 3.8 mg/g cumulative released amounts, respectively. A higher antioxidant activity was observed for 25% TA containing PC-L-PEI/TAH with 53.6 ± 5.3 µg/mL total phenol content and 0.48 ± 0.01 µmole Trolox equivalent/g. The minimum bactericidal concentration (MBC) of PC-L-PEIH and CC-L-PEIC networks against both E. coli (ATCC 8739) and Gram-positive B. subtilis (ATCC 6633) bacteria was determined at 5 mg/mL, whereas the MBC value of 10 mg/mL for CC-L-PEIH networks against the same bacteria was achieved.

Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use.

Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles.

A Review on Phyto-Therapeutic Approaches in Alzheimer's Disease.

Neurodegenerative diseases occur due to progressive and sometimes irreversible loss of function and death of nerve cells. A great deal of effort is being made to understand the pathogenesis of neurodegenerative diseases. In particular, the prevalence of Alzheimer's disease (AD) is quite high, and only symptomatic therapy is available due to the absence of radical treatment. The aim of this review is to try to elucidate the general pathogenesis of AD, to provide information about the limit points of symptomatic treatment approaches, and to emphasize the potential neurologic effects of phytocompounds as new tools as therapeutic agents for disease prevention, retardation, and therapy. This survey also covers the notable properties of herbal compounds such as their effects on the inhibition of an enzyme called acetylcholinesterase, which has significant value in the treatment of AD. It has been proven that phytopharmaceuticals have long-term effects that could protect nervous system health, eliminate inflammatory responses, improve cognitive damage, provide anti-aging effects in the natural aging process, and alleviate dementia sequelae. Herbal-based therapeutic agents can afford many advantages and can be used as potentially as new-generation therapeutics or complementary agents with high compliance, fewer adverse effects, and lower cost in comparison to the traditional pharmaceutical agents in the fight against AD.

Removal of Cd(II), Co(II), Cr(III), Ni(II), Pb(II) and Zn(II) ions from wastewater using polyethyleneimine (PEI) cryogels.

The removal of the target analytes, Cd(II), Co(II), Cr(III), Ni(II), Pb(II), and Zn(II) from contaminated waters was achieved using super porous polyethyleneimine (PEI) cryogels as adsorbent. The optimum values of the sample pH and contact time were determined as 4.0 and 90 min, respectively, for the removal of the analytes. The adsorption capacities of the sorbent were between 19.88 and 24.39 mgg-1 from 10 mL of 50 mgL-1 target metal ion solutions. The sorption kinetics of metal ions were fitted with the pseudo-second-order model. The adsorption isotherms of the target analytes into PEI cryogel were well-fitted to the Langmuir isotherm model as expected from the material homogeneity. The selectivity of the PEI cryogel in the presence of Na+, Ca2+, Mg2+, NO3-, K+ and Cl- ions even at high concentrations was tested, and the tolerance limits were satisfactory enough, e.g., the adsorption of the target analytes was even not affected in the presence of 2000 mgL-1 Ca2+, K+, Na+, Cl- and 5000 mgL-1 NO3- ions. The PEI cryogels were successfully utilized in different industrial wastewater samples that were spiked with a known amount of analytes. The removal of the analytes from wastewater samples was in the following ranges 91.94-99.86% for Cd(II), 89.59-99.89% for Co(II), 80.35-99.76% for Cr(III), 92.02-99.84% for Ni(II), 83.28-99.86% for Pb(II), and 82.94-98.24% for Zn(II), respectively. The presented novel removal strategy offers a selective, efficient, and easy application for target metal ions from industrial wastewater samples.

Nontoxic Natural Polymeric Particle Vehicles Derived from Hyaluronic Acid and Mannitol as Mitomycin C Carriers for Bladder Cancer Treatment.

Hyaluronic acid/mannitol (HA/MN)-based particles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the microemulsion crosslinking method were of 0.5-10 µm size with a zeta potential value of -36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ± 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ± 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 °C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 µg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 µg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 µg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 µg/mL destroyed almost all the cancer cells with 8 ± 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.

Therapeutic and Nutraceutical Effects of Polyphenolics from Natural Sources.

The prevalence of cardiovascular disease, oxidative stress-related complications, and chronic age-related illnesses is gradually increasing worldwide. Several causes include the ineffectiveness of medicinal treatment therapies, their toxicity, their inability to provide radical solutions in some diseases, and the necessity of multiple drug therapy in certain chronic diseases. It is therefore necessary for alternative treatment methods to be sought. In this review, polyphenols were identified and classified according to their chemical structure, and the sources of these polyphenol molecules are indicated. The cardioprotective, ROS scavenging, anti-aging, anticancer properties of polyphenolic compounds have been demonstrated by the results of many studies, and these natural antioxidant molecules are potential alternative therapeutic agents.

Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability.

Polyelectrolyte microgels derived from natural sources such as chondroitin sulfate (CS) possess considerable interest as therapeutic carriers because of their ionic nature and controllable degradation capability in line with the extent of the used crosslinker for long-term drug delivery applications. In this study, chemically crosslinked CS microgels were synthesized in a single step and treated with an ammonia solution to attain polyelectrolyte CS-[NH4]+ microgels via a cation exchange reaction. The spherical and non-porous CS microgels were injectable and in the size range of a few hundred nanometers to tens of micrometers. The average size distribution of the CS microgels and their polyelectrolyte forms were not significantly affected by medium pH. It was determined that the -34 ± 4 mV zeta potential of the CS microgels was changed to -23 ± 3 mV for CS- [NH4]+ microgels with pH 7 medium. No important toxicity was determined on L929 fibroblast cells, with 76 ± 1% viability in the presence of 1000 µg/mL concentration of CS-[NH4]+ microgels. Furthermore, these microgels were used as a drug carrier material for rosmarinic acid (RA) active agent. The RA-loading capacity was about 2.5-fold increased for CS-[R]+ microgels with 32.4 ± 5.1 µg/mg RA loading, and 23% of the loaded RA was sustainably release for a long-term period within 150 h in comparison to CS microgels. Moreover, RA-loaded CS-[R]+ microgels exhibited great antioxidant activity, with 0.45 ± 0.02 µmol/g Trolox equivalent antioxidant capacity in comparison to no antioxidant properties for bare CS particles.

Enhanced Bioactive Properties of Halloysite Nanotubes via Polydopamine Coating.

Halloysite nanotubes (HNT) were coated five times with dopamine (DOPA) in a tris buffer medium at pH 8.5 to acquire polydopamine-coated HNTs (PDOPA@HNT), e.g., PDOPA1@HNT, PDOPA3@HNT, and PDOPA5@HNT. Upon coating HNT with PDOPA, the surface area, pore volume, and pore size were decreased depending on the number of coatings. While the surface area of HNT was 57.9 m2/g, by increasing the number of coatings from 1 to 5, it was measured as 55.9, 53.4, 53.3, 47.4, and 46.4 m2/g, respectively. The isoelectric point (IEP) for HNTs was determined as 4.68, whereas these values are estimated as 2.31 for PDOPA1@HNTs, 3.49 for PDOPA3@HNT, and 3.55 for PDOPA5@HNT. Three different antioxidant studies were conducted for HNT and PDOPA@HNT, and the total phenol (TPC) value of HNT was found to be 150.5 ± 45.9 µmol gallic acid (GA) equivalent. The TPC values for PDOPA1@HNT, PDOPA3@HNT and PDOPA5@HNT coatings were found to be 405.5 ± 25.0, 750.0 ± 69.9, and 1348.3 ± 371.7 µmol GA equivalents, respectively. The Fe(II) chelation capacity of HNT was found to be 20.5% ± 1.2%, while the PDOPA1@HNT, PDOPA3@HNT and PDOPA5@HNT values were found to be 49.9 ± 6.5, 36.6 ± 12.7 and 25.4 ± 1.2%, respectively. HNT and PDOPA@HNTs inhibited the α-glucosidase (AG) enzyme to greater extents than acetylcholinesterase (AChE). As a result, the DOPA modification of HNTs was rendered to provide additional characteristics, e.g., antioxidant properties and higher AChE and AG enzymes inhibition capabilities. Therefore, PDOPA@HNTs have great potential as biomaterials.