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 poly(galacturonic acid) micro/nanogels with controllable degradation via tunable chemical crosslinking.

Here, one-pot labor-less preparation of two different polygalacturonic acid (PGA) micro/nanogel formulations, PGA-1 and PGA-2, by respectively crosslinking the PGA chains with divinyl sulfone (DVS) and trimethylolpropane triglycidyl ether (TMPGDE) were reported. Various crosslinker ratios, 2.5, 10, 50, and 100% were used for both crosslinkers to demonstrate the tunability of their degradation properties. The PGA micro/nanogels were found spherical-shaped porous particles in 0.5-5.0 µm size range by SEM. The hydrolytic degradation and stability of PGA micro/nanogels in pH 1.0, 7.4, and 9.0 buffer solutions can be controlled by changing the degree of crosslinking. Accordingly, 32 ± 8% and 36 ± 2% weight losses were attained for PGA-1-10% and PGA-2-10% micro/nanogels at pH 1, respectively, and 46 ± 6%, and 68 ± 6% degradations were determined at pH 7.4 within 4 weeks. However, no degradation was observed for both PGA-based micro/nanogel formulations prepared at 25% and 100% crosslinker ratios at all pH conditions. All PGA-based micro/nanogels were totally degraded within 7-10 days at pH 9.0. In the presence of pectinase and amyloglucosidase enzymes, all formulations of PGA micro/nanogels showed more than 80% degradation within 12 h. Furthermore, both PGA formulations showed no significant cytotoxicity against L929 fibroblast cells with 90% and above cell viability up to 250 mg/mL concentrations.

Bioaccessibility and bioavailability of selenium species in Se-enriched leeks (Allium Porrum) cultivated by hydroponically.

The Allium genus vegetables are of special interest since being potentially sources for selenium. In this study, the metabolization of selenite and selenate fortification at low and high levels in hydroponically cultivated Allium porrum (Leek) was investigated. The total Se analysis of nutritional solutions which was used in cultivation medium revealed that leeks had potential to accumulate Se above over 1000 mg/kg without any growth disturbance which was proved by comparing dry masses of control group with the ones fortified by Se species. Speciation analyses performed in edible parts which are leaves and stems showed that approximately 90% of total selenium was biotransformed into organo-selenium species in which MeSeCys and SeMet were found to be the most dominant in Se(IV) fortified leeks. However, selenate was found to be the most abundant species in edible parts of selenate fortified leeks especially at high levels. Although bioavailability rate of total selenium in selenate fortified leeks was found to be higher, lower amount of inorganic selenium and higher amount of MeSeCys were found to be bioavailable in Se(IV) fortified.

Chondroitin Sulfate-Based Cryogels for Biomedical Applications.

Cryogels attained from natural materials offer exceptional properties in applications such as tissue engineering. Moreover, Halloysite Nanotubes (HNT) at 1:0.5 weight ratio were embedded into CS cryogels to render additional biomedical properties. The hemolysis index of CS cryogel and CS:HNT cryogels was calculated as 0.77 ± 0.41 and 0.81 ± 0.24 and defined as non-hemolytic materials. However, the blood coagulation indices of CS cryogel and CS:HNT cryogels were determined as 76 ± 2% and 68 ± 3%, suggesting a mild blood clotting capability. The maximum% swelling capacity of CS cryogel was measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, at pH 1.0, pH 7.4 and pH 9.0, respectively, which were reduced to 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, for CS:HNT cryogel. It was found that CS cryogels can hydrolytically be degraded 41 ± 1% (by wt) in 16-day incubation, whereas the CS:HNT cryogels degraded by 30 ± 1 wt %. There is no chelation for HNT and 67.5 ± 1% Cu(II) chelation for linear CS was measured. On the other hand, the CS cryogel and CS:HNT cryogel revealed Cu(II) chelating capabilities of 60.1 ± 12.5%, and 43.2 ± 17.5%, respectively, from 0.1 mg/mL Cu(II) ion stock solution. Additionally, at 0.5 mg/mL CS, CS:HNT, and HNT, the Fe(II) chelation capacity of 99.7 ± 0.6, 86.2 ± 4.7% and only 11.9 ± 4.5% were measured, respectively, while no Fe(II) was chelated by linear CS chelated Fe(II). As the adjustable and controllable swelling properties of cryogels are important parameters in biomedical applications, the swelling properties of CS cryogels, at different solution pHs, e.g., at the solution pHs of 1.0, 7.4 and 9.0, were measured as 3587 ± 186%, 4014 ± 184%, and 3984 ± 113%, respectively, and the maximum selling% values of CS:HNT cryogels were determined as 1961 ± 288%, 2816 ± 192, 2405 ± 73%, respectively, at the same conditions. Alpha glucosidase enzyme interactions were investigated and found that CS-based cryogels can stimulate this enzyme at any CS formulation.

Poly(vinyl alcohol)-tannic Acid Cryogel Matrix as Antioxidant and Antibacterial Material.

The biocompatible, viscoelastic properties of poly(vinyl alcohol) (PVA) in combination with the antimicrobial and antioxidant natural polyphenolic, tannic acid (TA), and the natural flavonoid and antioxidant curcumin (Cur), were used in the preparation of PVA:TA and PVA:TA:Cur cryogel composites using cryotropic gelation to combine the individually beneficial properties. The effect of TA content on the antioxidant and antimicrobial activities of PVA:TA cryogel composites and the antioxidant activities of PVA:TA:Cur cryogel composites was determined using Trolox equivalent antioxidant capacity (TEAC) and total phenol content (TPC) assays, and were compared. The PVA:TA:Cur cryogel composite showed the highest antioxidant activity, with a TEAC value of 2.10 ± 0.24 and a TPC value of 293 ± 12.00. The antibacterial capacity of the PVA:TA and PVA:TA:Cur 1:1:0.1 cryogel composites was examined against two different species of bacteria, E. coli and S. aureus. It was found that the minimum inhibition concentration (MIC) value of the PVA:TA:Cur 1:1:0.1 cryogel composites varied between 5 and 10 mg/mL based on the type of microorganism, and the minimum bactericidal concentration (MBC) value was 20 mg/mL irrespective of the type of microorganism. Furthermore, the hemocompatibility of the PVA:TA cryogel composites was evaluated by examining their hemolytic and coagulation behaviors. PVA:TA 1:1 cryogels with a value of 95.7% revealed the highest blood clotting index value amongst all of the synthesized cryogels, signifying the potential for blood contacting applications. The release of TA and Cur from the cryogel composites was quantified at different pH conditions, i.e., 1.0, 7.4, and 9.0, and additionally in ethanol (EtOH) and an ethanol-water (EtOH:Wat) mixture. The solution released from the PVA:TA cryogels in PBS was tested for inhibition capability against α-glucosidase (E.C. 3.2.1.20). Concentration-dependent enzyme inhibition was observed, and 70 µL of 83 µg/mL PVA:TA (1:1) cryogel in PBS inhibited α-glucosidase enzyme solution of 0.03 unit/mL in 70 µL by 81.75 ± 0.96%.

A primary reference method for the characterization of Cd, Cr, Cu, Ni, Pb and Zn in a candidate certified reference seawater material: TEA/Mg(OH)2 assisted ID3MS by triple quadrupole ICP-MS/MS.

A certified reference seawater material (CRM), UME CRM 1206 which was sampled from the Marmara Sea (40 31,423 N; 027 11, 333 E) with 27 psu of salinity is about to be released by Inorganic Analysis Laboratory of TÜBITAK National Metrology Institute (UME). This paper represents the characterization measurements of Cd, Cr, Cu, Ni, Pb and Zn in this CRM. The use of a reference method by a single laboratory is one of the options for the characterization of a candidate CRM according to ISO 17034 [39]. This approach is used throughout this study with an introduction of a primary reference method. For this purpose, combination of triethylamine assisted Mg(OH)2 co-precipitation and triple isotope dilution mass spectrometry (TEA/Mg(OH)2-ID3MS) were developed and validated. This optimized co-precipitation protocol provided the recovery of target analytes within the range of 72%-92% which was the main advantage of TEA/Mg(OH)2 method especially for Cd, Ni, Cu and Zn compared to NH4OH assisted co-precipitation. Analytical performance of TEA/Mg(OH)2-ID3MS were investigated under the optimum conditions. The results for matrix certified reference material were found to be not significantly different from the certified values based on the comparison of the results and certified values within their combined uncertainties. On the other hand, intermediate precision and repeatability of the developed method were found to be in the range of 0.34%-0.90% and 0.09%-0.49%, respectively. This study reports characterization measurements with their expanded uncertainties (k = 2) as 0.4327 ± 0.0071 ng/g for Cd, 2.442 ± 0.033 ng/g for Cr, 1.018 ± 0.012 ng/g for Cu, 4.568 ± 0.037 ng/g for Ni, 1.068 ± 0.016 ng/g for Pb and 8.521 ± 0.075 ng/g for Zn where the intermediate precision was found to be the main contributor to measurement uncertainty budget of TEA/Mg(OH)2-ID3MS method for each analyte.

Traceable and accurate quantification of iron in seawater using isotope dilution calibration strategies by triple quadrupole ICP-MS/MS: Characterization measurements of iron in a candidate seawater CRM.

Accurate quantification of iron is crucial for the characterization of a candidate seawater certified reference material. Isotope dilution mass spectrometry as a primary method is one of the option for this purpose. In this study, triethylamine (TEA) assisted Mg(OH)2 co-precipitation is developed and combined with isotope dilution mass spectrometry for the characterization of candidate certified reference material, UME CRM 1206. The analytical protocol of co-precipitation was optimized to achieve reproducible yields of ~100% Fe with high salt rejection (residual salinity ~0.003%). Three calibration strategies, single, double and triple isotope dilution mass spectrometry (IDMS) coupled with co-precipitation were investigated in terms of metrological aspects. The determination of Fe was carried out by ICP-MS with tandem configuration (ICP-MS/MS) using NH3/He cell gas which was optimized for the minimum background equivalence concentration to be able to measure highly accurate 56Fe/57Fe ratio with the highest possible sensitivity. The background corrected typical procedural blank levels and limit of detection calculated based on three times the standard deviation of blanks were found as 9 ng/kg (0.16 nM) and 11 ng/kg (0.20 nM) for single IDMS, respectively. Trueness of the developed analytical methods has been demonstrated using CASS-6 and NMIA MX014 with complete and very precise recoveries. SI-traceable values with combined uncertainty (k = 2) were obtained for single, double and triple IDMS as (12.70 ±â€¯0.16) ng/g, (12.728 ±â€¯0.084) ng/g and (12.732 ±â€¯0.062) ng/g, respectively. The relative combined uncertainty for each approach was calculated as 0.64%, 0.33% and 0.24%, respectively.

Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery.

Porous and biodegradable hyaluronic acid (HA) nanogel and their copolymeric forms with sucrose (Suc), HA:Sucrose (HA:Suc) nanogels, were synthesized by employing glycerol diglycidyl ether (GDE) as crosslinker with a single step reaction in surfactant-free medium. The size of the nanogels was determined as 150 ±â€¯50 nm in dried state from SEM images and found to increase to about 540 ±â€¯47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.07 ±â€¯2.4 and 32.30 ±â€¯6.1 m2/g with porosities of 3.58 ±â€¯1.8, and 9.44 ±â€¯3.1 nm via BET analysis, respectively. The zeta potentials for HA and HA:Suc nanogels were measured as -33 ±â€¯1.4 and - 30 ±â€¯1.2 mV, respectively. The thermal degradation of both types of nanogels revealed similar trends, while hydrolytic degradation of the nanogels was about 22.7 ±â€¯0.2 wt% in 15 days. Both HA and HA:Suc nanogels were stable in blood up to 250 µg/mL concentration with approximately 0.5 ±â€¯0.1% hemolysis ratio and 76 ±â€¯12% blood clotting indices, respectively. Finally, these nanogels were used as a sustained slow-release or long-term delivery system over 2 days for a hydrophobic cancer drug, 3­((E)­3­(4­hydroxyphenyl)acryloyl)­2H­chromen­2­on (A#) established by our group. The nanogels successfully delivered the model drug A at 10.43 ±â€¯2.12 mg/g for 2 days.

A novel analytical approach for the determination of parathion methyl in water: quadrupole isotope dilution mass spectrometry-dispersive liquid-liquid microextraction using multivariate optimization.

Dispersive liquid-liquid microextraction was coupled with quadruple isotope dilution mass spectrometry for the sensitive and accurate determination of parathion methyl in water. The two methods were complementary to each other, with DLLME preconcentrating the analyte for trace determination, and ID4MS maintaining the integrity of the method's accuracy and precision. An experimental design was used to optimize the extraction process. The results from the design were evaluated with the analysis of variance to determine the statistical significance of the main factors of extraction and interaction effects of these factors. A three-point calibration blend and sample blend were prepared gravimetrically by spiking with isotopically labelled parathion methyl. All four blends were left to equilibrate for three hours, after which they were preconcentrated under the optimum extraction conditions. The percent recovery recorded by this method was 99.9%, and the percent relative standard deviation was 0.32%. These results validated the accuracy and precision of the combined method.