Search

This study describes the formation of cellulose based polyelectrolyte charge complexes on the surface of biodegradable polycaprolactone (PCL) thin films. Anionic sulphated cellulose (CS) and protonated cationic amino cellulose (AC) were used to form these complexes with a layer-by-layer coating technique. Both polyelectrolytes were analyzed by charge titration methods to elucidate their pH-value dependent protonation behavior. A quartz crystal microbalance with dissipation (QCM-D) in combination with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to follow the growth, stability and water content of up to three AC/CS bi-layers in aqueous environment. This was combined with coagulation studies on one, two and three bilayers of AC/CS, measuring the thrombin formation rate and the total coagulation time of citrated blood plasma with QCM-D. Stable mixed charged bilayers could be prepared on PCL and significantly higher masses of AC than of CS were present in these complexes. Strong hydration due to the presence of ammonium and sulphate substituents on the backbone of cellulose led to a significant BSA repellent character of three bilayers of AC/CS coatings. The total plasma coagulation time was increased in comparison to neat PCL, indicating an anticoagulative nature of the coatings. Surprisingly, a coating solely composed of an AC layer significantly prolonged the total coagulation time on the surfaces although it did not prevent fibrinogen deposition. It is suggested that these cellulose derivative-based coatings can therefore be used to prevent unwanted BSA deposition and fibrin clot formation on PCL to foster its biomedical application., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: In this work, low-molecular-weight sulfoethyl chitosan (SECS) was used as a model template for the generation of silver core-shell nanoparticles with high potential as anticoagulants for medical applications., Materials and Methods: SECS were synthesized by two reaction pathways, namely Michael addition and a nucleophilic substitution with sodium vinylsulfonate or sodium 2-bromoethanesulfonate (NaBES). Subsequently, these derivatives were used as reducing and capping agents for silver nanoparticles in a microwave-assisted reaction. The formed silver-chitosan core-shell particles were further surveyed in terms of their anticoagulant action by different coagulation assays focusing on the inhibition of either thrombin or cofactor Xa., Results: In-depth characterization revealed a sulfoalkylation of chitosan mainly on its sterically favored O 6-position. Moreover, comparably high average degrees of substitution with sulfoethyl groups (DS SE ) of up to 1.05 were realized in reactions with NaBES. The harsh reaction conditions led to significant chain degradation and consequently, SECS exhibits masses of <50 kDa. Throughout the following microwave reaction, stable nanoparticles were obtained only from highly substituted products because they provide a sufficient charge density that prevented particles from aggregation. High-resolution transmission electron microscopy images reveal that the silver core (diameter ~8 nm) is surrounded by a 1-2 nm thick SECS layer. These core-shell particles and the SECS itself exhibit an inhibiting activity, especially on cofactor Xa., Conclusion: This interesting model system enabled the investigation of structure-property correlations in the course of nanoparticle formation and anticoagulant activity of SECS and may lead to completely new anticoagulants on the basis of chitosan-capped nanoparticles., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Flavonoid glycosides have many beneficial effects on health, but these bioactivities tend to decrease after oral administration owing to their poor lipophilicity. In this study, a facile whole-cell-based method was developed for selective preparation of monoester or diester of troxerutin, a flavonoid derivative. In addition, the bioavailabilities and antioxidant properties of troxerutin and its acylated derivatives were also investigated in cells., Results: Pseudomonas aeruginosa and Pseudomonas stutzeri cells showed high catalytic efficiency (substrate conversion > 90%) and different preferences for troxerutin, resulting in the production of its monoester (TME) and diester (TDE), respectively. The logP values of troxerutin, TME, and TDE were - 2.04 ± 0.10, - 0.75 ± 0.08, and 1.51 ± 0.05 and their P app values were 0.34 × 10 -6  ± 0.05, 0.99 × 10 -6  ± 0.12, and 1.54 × 10 -6  ± 0.17 cm/s, respectively. The results of hydroxyl radical, ABTS, and ORAC assays indicated that the antiradical activities of acylated derivatives did not exceed that of troxerutin, but showed higher inhibition effects upon 2,2'-azobis(2-amidinopropane) dihydrochloride-induced erythrocyte hemolysis than that of troxerutin (P < 0.05)., Conclusion: A facile and efficient whole-cell biocatalysis method was developed to synthesize troxerutin-acylated derivatives, markedly enhancing the bioavailability and antioxidant activities of troxerutin in cells. Additionally, the mechanism underlying the observed difference in the antioxidant activities of troxerutin and its esters was ascribed to both their free radical scavenging abilities and distribution on the cell membrane surface.

Objective: To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS)., Methods: Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed., Results: One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15-30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD., Conclusion: Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13 CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO 3 ∙Pyridine (SO 3 ∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of -SO 3 /-OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO 3 ∙Py complex was added to DMF/LiCl with -SO 3 /-OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 μg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.