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.

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.

Titanium platelet-rich fibrin (T-PRF) as high-capacity doxycycline delivery system.

OBJECTIVES: Titanium platelet-rich fibrin (T-PRF), a second-generation autogenous blood concentrate with tough and thick fibrin meshwork activated by a titanium tube, was used as a drug carrier for doxycycline (Doxy) by injection. The objective of this study is to evaluate the loading capacity of T-PRF, release kinetics of doxycycline-loaded T-PRF, and its antibacterial effects against S. aureus and P. aeruginosa. MATERIALS AND METHODS: The T-PRF and collagen were loaded with Doxy as T-PRF/Doxy and Collagen/Doxy, and their release and antibacterial activities against S. aureus and P. aeruginosa were investigated. Chemical characterization and morphological analysis were performed. RESULTS: In comparison with collagen, approximately sevenfold more Doxy, 281 mg/g, was loaded into T-PRF. It was found that 25% of the loaded Doxy was released from T-PRF compared to only 12% from collagen within 72 h. The largest inhibition zone diameter (IZD) was observed for T-PRF/Dox with 32 ± 6 mm and 37 ± 5 mm for P. aereginosa and S. aureus, respectively. However, only 10 ± 5 mm and 10 ± 6 mm IZD were observed for bare T-PRF, and no inhibition zone was observed for the Collagen/Doxy group. A dense fibrin structure was visualized on SEM images of the T-PRF/Doxy group compared to the T-PRF group. CONCLUSIONS: T-PRF has higher Doxy loading capacity and long-acting antibacterial effects compared to collagen. T-PRF was shown to have potential autogenous long-term drug-carrying capability for doxycycline. Also, the potential fibrinophilic properties of Doxy were observed to strengthen the structure of T-PRF. CLINICAL RELEVANCE: T-PRF is an autogenous drug career with high loading capacity and extended antibacterial effects for doxycycline. Doxycycline molecules can be visible on T-PRF fibers. This study suggests that T-PRF/Dox could be used as a proper antibiotic delivery device in the treatments of periodontitis and peri-implantitis.

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.

Versatile Fluorescent Carbon Dots from Citric Acid and Cysteine with Antimicrobial, Anti-biofilm, Antioxidant, and AChE Enzyme Inhibition Capabilities.

Nanostructured fluorescent particles derived from natural molecules were prepared by a green synthesis technique employing a microwave method. The precursors citric acid (CA) and cysteine (Cys) were used in the preparation of S- and N-doped Cys carbon dots (Cys CDs). Synthesis was completed in 3 min. The graphitic structure revealed by XRD analysis of Cys CDs dots had good water dispersity, with diameters in the range of 2-20 nm determined by TEM analysis. The isoelectric point of the S, N-doped CDs was pH value for 5.2. The prepared Cys CDs displayed excellent fluorescence intensity with a high quantum yield of 75.6 ± 2.1%. Strong antimicrobial capability of Cys CDs was observed with 12.5 mg/mL minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria with the highest antimicrobial activity obtained against Staphylococcus aureus. Furthermore, Cys CDs provided total biofilm eradication and inhibition abilities against Pseudomonas aeruginosa at 25 mg/mL concentration. Cys CDs are promising antioxidant materials with 1.3 ± 0.1 µmol Trolox equivalent/g antioxidant capacity. Finally, Cys CDs were also shown to inhibit the acetylcholinesterase (AChE) enzyme, which is used in the treatment of Alzheimer's disease, even at the low concentration of 100 µg/mL.

Self-Crosslinked Ellipsoidal Poly(Tannic Acid) Particles for Bio-Medical Applications.

Self-crosslinking of Tannic acid (TA) was accomplished to obtain poly(tannic acid) (p(TA)) particles in single step, surfactant free media using sodium periodate (NaIO4) as an oxidizing agent. Almost monodisperse p(TA) particles with 981 ± 76 nm sizes and -22 ± 4 mV zeta potential value with ellipsoidal shape was obtained. Only slight degradation of p(TA) particles with 6.8 ± 0.2% was observed at pH 7.4 in PBS up to 15 days because of the irreversible covalent formation between TA units, suggesting that hydrolytic degradation is independent from the used amounts of oxidation agents. p(TA) particles were found to be non-hemolytic up to 0.5 mg/mL concentration and found not to affect blood clotting mechanism up to 2 mg/mL concentration. Antioxidant activity of p(TA) particles was investigated by total phenol content (TPC), ferric reducing antioxidant potential (FRAP), trolox equivalent antioxidant capacity (TEAC), total flavanoid content (TFC), and Fe (II) chelating activity. p(TA) particles showed strong antioxidant capability in comparison to TA molecules, except FRAP assay. The antibacterial activity of p(TA) particles was investigated by micro-dilution technique on E. coli as Gram­negative and S. aureus as Gram-positive bacteria and found that p(TA) particles are more effective on S. aureus with over 50% inhibition at 20 mg/mL concentration attained.

Delivery of Small Molecule EF2 Kinase Inhibitor for Breast and Pancreatic Cancer Cells Using Hyaluronic Acid Based Nanogels.

PURPOSE: To evalauted natural polymeric biomaterials including hyaluronic acid (HA) and its copolymeric form HA:Suc nanoparticles (NPs) as drug carrier systems for delivery of hydrophobic small molecule kinase EF2-kinase inhibitor in breast and pancreatic cancer cells. METHODS: In vitro cellular uptake studies of Rhodamine 6G labaled HA:Suc nanoparticles were evaluated by using flow cytometry analysis and fluorescent microscopy in breast (MDA-MB-231 and MDA-MB-436) and pancreatic cancer cells (PANC-1 and MiaPaca-2). Besides, in vitro release study of compound A (an EF2-kinase inhibitor) as a model hydrophobic drug was performed in the cancer cells. RESULTS: These biological evaluation studies indicated that HA and HA:Suc NPs provided a highly effective delivery of compound A were into breast and pancreatic cancer cells, leading to significant inhibition of cell proliferation and colony formation of breast and pancreatic cancer cells. CONCLUSION: HA-sucrose NPs incorporating an EF2-Kinase inhibitor demonstrate significant biologic activity in breast and pancreatic cancer cells. This is the first study that shows natural polymeric drug carriers succesfully deliver a hydrofobic cancer drug into cancer cells. Graphical Abstract Nanoparticles based on HA:Suc are effective in delivering hydrofobic cancer drugs in breast and pancreatic cancers.

Tunable Friction Through Stimuli Responsive Hybrid Carbon Microspheres.

We explore the use of poly(N-isopropylacrylamide) (PNIPAm)-grafted carbon microspheres (CM) dispersed in water as a stimulus-responsive lubricant. A critical concentration between 3 and 5 mg/mL of PNIPAm-grafted CM is needed to achieve low friction (coefficient of friction ∼ 0.04) at room temperature between borosilicate and silicon surfaces. An increase in the temperature of the system above the lower critical solution temperature (LCST) causes the aggregation of PNIPAm-grafted CM which leads to an increase in friction forces. The process is not immediately reversible unless the lubricant is sonicated so as to redisperse the aggregates. This work provides insight into the rolling friction mechanism and demonstrates the importance of particle singlets in achieving effective lubrication through a rolling mechanism.

Nitrogen and Sulfur Doped Carbon Dots from Amino Acids for Potential Biomedical Applications.

Nitrogen (N-) and sulfur (S-) doped carbon dots (CDs) were synthesized in a single step in a few min, 1-4 min via microwave technique from five different types of amino acids viz. Arginine (A), Lysine (L), Histidine (H), Cysteine (C), and Methionine (M). These amino acid derived N- and/or S- doped CDs were found to be in spherical shapes with 5-20 nm particle size range determined by Transition Electron Microscope (TEM) images and Dynamic Light Scattering (DLS) measurements. Thermal degradation, functional groups, and surface potential of the CDs were determined by Thermogravimetric Analysis (TGA), FT-IR spectroscopy, and zeta potential measurements, respectively. Although the zeta potential value of Cysteine derived CD (C-CD) was measured as -7.45±1.32 mV, the zeta potential values of A-CD, L-CD, H-CD, and M-CD particles were measured as +2.84±0.67, +2.61±1.0, +4.10±1.50 and+2.20±0.60 mV, respectively. Amongst the CDs, C- CDs was found to possess the highest quantum yield, 89%. Moreover, the blood compatibility test of CDs, determined with hemolysis and blood clotting tests was shown that CDs at 0.25 mg/mL concentration, CDs has less than 5% hemolysis ratio and higher than 50% blood clotting indexes. Furthermore, A-CD was modified with polyethyleneimine (PEI) and was found that the zeta potential values was increased to +34.41±4.17 mV (from +2.84±0.67 mV) inducing antimicrobial capability to these materials. Minimum Inhibition Concentration (MIC) of A-CD dots was found as 2.5 mg/mL whereas the PEI modified A-CDs, A-CD-PEI was found as 1 mg/mL against Escherichia coli ATCC 8739 (gram -) and Staphylococcus aureus ATCC 6538 (gram +) bacteria strains signifying the tunability of CDs.

Removal of arsenate and dichromate ions from different aqueous media by amine based p(TAEA-co-GDE) microgels.

In this work, microgels based on tris(2-aminoethyl) amine (TAEA) and glycerol diglycidyl ether (GDE) via simple microemulsion polymerization was prepared as p(TAEA-co-GDE) microgels were used as adsorbent for removal of dichromate (Cr (VI)) and arsenate (As (V)) ions from different aqueous environments. The p(TAEA-co-GDE) microgels were demonstrated very efficient adsorption capacity for Cr (VI), and As (V) that are 164.98 mg/g, and 123.64 mg/g from distilled (DI) water, respectively. The effect of the medium pH on the adsorption capacity of p(TAEA-co-GDE) microgels for Cr (VI) and As (V) ions were investigated. The maximum adsorption capacity was obtained at pH 4.0 for both ions with maximum adsorbed amounts of 160.62, and 98.72 mg/g, respectively. In addition, the microgels were also shown moderate adsorption capacity for Cr (VI) and As (V) from other water sources; tap water with 115.18 mg/g and 82.86 mg/g, sea water with 64.24 mg/g and 46.88 mg/g and creek water with 73.52 mg/g and 59.33 mg/g, respectively. Moreover, the increase in adsorbent dose from 0.025 to 0.125 g enhanced % adsorption of Cr (VI) from 54.13 to 98.03, and As (V) from % 26.72-98.70, respectively. For the adsorption process Langmuir and Freundlich adsorption isotherms were applied and found that Langmuir adsorption isotherm with R2 value of 0.99 for both the metal ions are suitable. Moreover, the experimental adsorption capacities of Cr (VI) and As (V) were found very close to the theoretical values calculated from Langmuir adsorption isotherm. More importantly, the microgels were made magnetic responsive to recover them easily from adsorption medium for reuse studies by applying external magnetic field with little decrease in adsorption capacity. Additionally, reusability of p(TAEA-co-GDE) microgels was also evaluated for adsorption of Cr (VI) and As (V) from DI water.

Fast removal of high quantities of toxic arsenate via cationic p(APTMACl) microgels.

Hydrogels are resourceful materials and can be prepared in different morphology, size, surface charge and porosity adopting different polymerization techniques and reaction conditions. The cationic poly(3-acrylamidopropyl)trimethylammonium chloride (p(APTMACl)) microgels were synthesized by photo-initiated inverse suspension polymerization technique. These microgels were utilized as absorbents for the removal of toxic arsenate (As) from different aqueous environments. The experimental parameters affecting absorption efficiency were investigated, and it was demonstrated that these types of microgels are highly efficient in removing arsenate anions from different aqueous environments compared to the previously reported bulk hydrogel, and cryogel of the same material. A removal efficiency of approximately 97.25% was obtained by immersing 0.5 g microgel in 250 ppm 100 mL solution of arsenate anions for 60 min. Both Langmuir and Freundlich adsorption isotherms were applied to adsorption of arsenate anions by p(APTMACl) microgels, and the Langmuir isotherm was a better representation of the adsorption of arsenate with a high value of R(2) (0.9982). Furthermore, mag-p(APTMACl) microgels were synthesized for the adsorption of arsenate anions to provide easy removal of the microgel composite by using an externally applied magnetic field. Furthermore, re-usability of the p(APTMACl) microgels was also investigated for the adsorption of arsenate anions.

The use of superporous p(3-acrylamidopropyl)trimethyl ammonium chloride cryogels for removal of toxic arsenate anions.

Poly((3-Acrylamidopropyl)trimethylammonium chloride) (p(APTMACl)) cryogels were used as a superporous polymer network for the removal of toxic arsenate anions from an aqueous medium. The fast swelling in water, in about 7 s, was shown to be very useful leading to fast arsenate adsorption by p(APTMACl) cryogels within 30 min in comparison to 12 h for bulk common p(APTMACl) hydrogels. A maximum adsorption capacity of about 120 (mg/g) arsenate was obtained for p(APTMACl) cryogels. Both the Langmuir and Freundlich adsorption isotherms were applied for adsorption of arsenate anions by p(APTMACl) cryogels, and it was observed that the adsorption of arsenate anions by p(APTMACl) cryogels are represented better via Langmuir adsorption isotherm providing the R(2) value of 0.998. Furthermore, mag-p(APTMACl) cryogels were synthesized, and shown to be very useful in the fast removal of toxic arsenate anions. The mag-p(APTMACl) cryogels including the adsorbed arsenate were removed by an externally applied magnetic field, with some reduction in the arsenate ion adsorption capacity. It was also further demonstrated that p(APTMACl) cryogels can be reused in the adsorption of arsenate 5 times from aqueous environments without significant loss of adsorption capacity, from 113.47 ± 9 to 102.67 ± 6 mg/g.

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.

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.

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.

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.

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.

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.

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.

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.