Cross Linkage Research Articles

Ultrasound-induced Microencapsulation of Simvastatin for Gastro Retention and Controlled Delivery

The objective of this study is to demonstrate an effective technique with potential for commercialization for microsphere production. Ultrasound-assisted ionic gelation of sodium alginate was used to encapsulate simvastatin. Chitosan was used as a mucoadhesive polymer for gastro-retention of microsphere. Sodium alginate solution was sonicated using probe sonicator at a frequency of 20±3 KHz and ultrasonic power of 130 W with an input voltage range of 170-270 AC, 50 Hz, at a temperature of 50°. The influence of ultrasound waves on drug entrapment efficiency, yield and particle size dispersion was studied in comparison to mechanical stirring method. Mucoadhesiveness, release pattern and kinetics of drug release were also characterized. Ultrasound treatment caused small fissures and depressions on the surface of alginate as evidenced in SEM. Ultrasound of 20±3 KHz for 12 min duration was the optimum frequency and time in the experimental set up to obtain microspheres with uniform and smaller microparticles. The encapsulation efficiency of simvastatin was directly proportional to the sonication effect, concentration of alginate and extent of its cross linkage with calcium ions. DSC studies revealed that ultrasound treatment did not alter the structural integrity of the drug component. Formulation was found to be dissolution efficient and drug release pattern was concentration dependent, which followed non-Fickian diffusion mechanism with an ‘n’ value of 0.8. Therefore, it could be concluded that ultrasound can be used as an efficient technology to develop drug-entrapped microsphere for controlled delivery.

Cross linkage between quality of sleep and neurologic conditions in age-diverse populations

Sleep medicine is inextricably interwoven with neurological health, be it in the young, adult, or geriatric population. Recent studies have highlighted its clinical benefit in autism, attention deficit hyperactivity disorder, traumatic brain injury, headache, epilepsy, multiple sclerosis, neuromuscular disease, stroke, and Alzheimer's disease. The tool of sleep health optimization may provide significant benefit and transform outcome and prognosis, and may also help yield a greater insight into many of these neurologic conditions.

Preparation of Water-Repellent Monomolecular Films by CF<sub>4</sub> Plasma Treatment on Hydrocarbon Monolayers

Hydrocarbon monomolecular films were prepared on a glass slide with a chemical adsorption technique. Water-repellent fluorocarbon monomolecular films were prepared by CF4 plasma treatment on the chemically adsorbed hydrocarbon monomolecular films. However, the monomolecular films were usually removed by sputtering when the CF4 plasma was treated, because CF4 plasma contains ions of the fluorocarbon fragments, not only its radicals. Therefore, fluorocarbon ions were removed from the plasma by mesh connected to the earth, and then only fluorocarbon radicals were used for treatment in order to prevent the monomolecular film from being removed. Fourier-transform infrared reflection absorption spectroscopy (FTIR-RAS) revealed that the hydrocarbon groups or hydrogens of the hydrocarbon monomolecular film were substituted with fluorocarbon or a fluorocarbon radical. In addition, the water drop contact angle of the film slightly increased by the treatment. It was demonstrated that water-repellent monomolecular films can be prepared by CF4 plasma treatment on hydrocarbon monolayers. Thus, the plasma treatment technique may be useful into preparing the highly durable fluorinated monomolecular films with the cross linkage inter adsorbed molecules in the monolayer films.

Popliteal Artery Aneurysm in Women

Ninety-five per cent of those operated on for popliteal artery aneurysm (PA) are men. Thus, PAs in women are difficult to investigate. The aim was to study the disease in women. Women treated for PA in 1987-2012, prospectively registered in the Swedish vascular registry, Swedvasc, supplemented by case records, were compared with the larger male cohort. Survival was determined through cross linkage with the National Population Registry. 1509 patients (men and women), 1872 legs, were identified; of these 74 patients (4.9%) were women, 81 legs (4.3%). The median age was 70 years in women versus 69 in men. Twenty-nine centres operated on women (range 1-7 women/centre). There were no time trends in the proportion of women operated on (p=.5). Bilateral PA occurred in 9.5% of women and 27.0% of men (p=.002). For symptomatic aneurysms, there was a larger proportion of small aneurysms (<2cm) among women than men (24% vs. 8%, p=.005), there was no such difference in asymptomatic aneurysms. Distribution between asymptomatic and symptomatic PA was 31% versus 69%, similar to men. The prevalence of concomitant aneurysms in the aorto-iliac and femoral arteries, and the frequency of presenting symptoms were similar compared with men. Three PA were ruptured (3.7%). Thrombolysis was used in 23 of 45 legs treated for acute ischaemia (51%). Eight legs were treated with endovascular stent grafts (9.8%), compared with 7.9% in men (p=.5). Seven legs were amputated (8.6%). Crude survival was similar to men. PA is similar in women and men, but bilateral disease was less common in women and symptomatic PA were more often <2cm in diameter. Women had the same survival as men, despite women generally having better life expectancy. Although the largest series ever published on women with PA, the sample size is small, making it prone to type II statistical error.

Functional microporous polymers through Cu-mediated, free-radical polymerization of buckminster [60] fullerene

We report a family of novel microporous polymers constructed through covalent cross linkage of the buckyball and linear dialkyne through Cu-mediated, one-pot synthesis. A novel functionalization-polymerization pathway is described whereby Cu-mediated free radical species, generated in-situ, triggered multiple additions of the ditopic alkyne to C60. The multi-functionalized C60 species act as nodes that afforded microporous networks on extension through proper bridges. Solid-based spectroscopy techniques allowed identification of the chemical composition of the polymers, while gas sorption measurements were utilized to probe the microporosity, surface area, and pore size distribution of the constructed solids. Electron paramagnetic resonance (EPR) spectroscopy demonstrated a free radical pathway for the polymerization reaction. In addition to a relatively unstable diisopropyl nitroxide radical, EPR revealed a quasi-stable, C60-derived, organic radical that exhibits an unusually intense MW absorption and long lifetime at room temperature (>5 days). Two of the reported solids were further investigated and demonstrated activity for electrochemical CO2 reduction. We present here a simple and versatile pathway for using C60 as a building block in the construction of novel materials, and potentially porous magnetic materials encompassing diverse functionality and manipulable properties.

Long-term Outcome after Thrombolysis for Acute Lower Limb Ischaemia

The purpose was to study long-term outcome after thrombolysis for acute arterial lower limb ischaemia, and to evaluate the results depending on the underlying aetiology of arterial occlusion. This was a retrospective study of patients entered into a prospective database. Patients were identified in prospective databases from two vascular centres, including a large number of variables. Case records were analysed retrospectively. Through cross linkage with the Population Registry 100% accurate survival data were obtained. Between January 2001 and December 2013, 689 procedures were included. The aetiology of ischaemia was graft/stent/stent graft occlusion in 39.8%, arterial thrombosis in 27.7%, embolus in 25.1% and popliteal aneurysm in 7.4%. The mean follow-up was 59.4 months (95% CI, 56.1-62.7), during which 32.9% needed further re-interventions, 16.4% underwent amputation without re-intervention, and 50.7% had no re-intervention. The need for re-intervention during follow-up was 48.0% in the graft/stent occlusions group, 34.0% of the popliteal aneurysm group, 25.4% in the thrombosis group, and 16.3% in the embolus group (p<.001). The overall primary patency rates were 69.1% and 55.9% at 1 and 5 years, respectively. Primary patency at 5 years was higher for the embolus group (83.3%, p=.002) and lower for the occluded graft/stent group (43.3%, p<.001). Secondary patency rates were 80.1% and 75.2% at 1 and 5 years, respectively, without difference between the subgroups. The amputation rate was lower in the embolic group at 1 and 5 years (8.1% and 11.1%, respectively, p=.001). Survival was higher in the group with occluded popliteal aneurysms at 5 years (83.3%, p=0.004). Amputation free survival was 72.1% and 45.2% at 1 and 5 years; lower in the occluded graft/stent group at five years (37.9%, p=.007). Intra-arterial thrombolytic therapy achieves good medium and long-term clinical outcome, reducing the need of open surgical treatment in most patients.

3D Stereolithography of Polymer Composites Reinforced with Orientated Nanoclay

Polymer parts fabricated by 3D stereolithography (SL) tend to have much lower mechanical properties compared to their counterparts fabricated by conventional methods. Furthermore, due to cross linkage among polymer chains in the thermoset polymers, the SL printed parts tend to have low elongation and experience brittle fracture during failure. Various types of fillers have been added into photopolymer to improve the mechanical properties, with most of them being randomly dispersed. In this study, montmorillonite nanoclays (plate-shaped) are first exfoliated and homogenously dispersed in the photopolymer via several mixing steps, including sonification. After which, using the photopolymer dispersed with nanoclays in a bottom-up SL, the descending of build platform into the resin tank during the printing process provides a downward force to orientate the plate-shaped nanoclays in each layer. The nanoclays will be immobilized during photopolymerization upon ultra-violent (UV) exposure, thus maintaining their orientation and alignment. This process drastically improves the elongation by more than 100% and enhances the tensile stress and Young’s Modulus in the X-Y plane. This paper will also discuss the dispersion, alignment, size and loadings of the montorillonite nanoclays. This new approach will open up possibilities of printing high performance parts using stereolithography, increasing its functionality.

Role of collagen cross linking in keratoconus

Background: Corneal grafting is associated inherent risks that could result in permanent loss of vision and significantly affect the quality of life. Corneal collagen cross linking is a new technique that can either prevent corneal transplantation or delay the progress of keratoconus. Advanced tools of the day can measure the contours of the cornea perfectly to adopt the new technology of corneal collagen cross linking. Objective: To evaluate the outcome of the collagen cross linkage using riboflavin 0.1% and ultraviolet A radiation of wavelength 370 nm. Methods: This prospective interventional trial of corneal collagen cross-linking was carried out in 50 eyes of 30 patients with progressive keratoconus from January 2013 to July 2014. The paired t test was used to check the significance of the difference between 2 dependent groups. The level of statistical significance was set at P<0.05 Results: 80% of the study subjects in the age group of 16 to 25 years. 60% of the study group was males. 34% of the study group was with severing keratoconus. Based on pachymetry findings, 84% of the study group classified as moderate keratoconus. Conclusion: Visual acuity improved in keratoconus patients by 1.5 lines of Snellen's equivalent, henceforth CXL can be treatment modality for visual improvement along with other techniques.

Comparison of analgesic effect of preoperative topical Diclofenac versus Ketorolac on postoperative pain after Corneal Collagen Cross Linkage.

Objective:To compare post-operative pain relieving effect of topical diclofenac 0.1% versus ketorolac 0.5% in Corneal Collagen Cross Linking (CXL) for patients diagnosed with keratoconus.Methods:This randomized controlled trial was carried out for six months from October 2016 to March 2017. We included young patients having keratoconus with k-readings greater than 47D and central corneal thickness more than 400 microns. All the patients received single dose one drop of topical diclofenac 0.1% to (Group-A) and ketorolac 0.5% to (Group-B) 30 minutes in advance of the corneal collagen cross linking (CXL) procedure. The CXL was performed with topical 0.1% riboflavin eye drops in 20% dextran as a photo sensitizer. After 36 hours of the CXL procedure, the postoperative intensity of pain was assessed verbally by patients with the help of visual analog scale (VAS) numbers from zero to five where 0 designated no pain & 5 symbolized worst pain.Results:The study comprised sixty eyes of forty one patients. Out of total 16 were male while 25 female patients. The mean age of the patients was 24.27 ± 2.93 years (range 20 to 29 years). In the conclusive analysis, diclofenac 0.1% was used on 30 patients in Group-A and ketorolac 0.5% on 30 subjects in Group-B. Pain relieving scores in Group-A (diclofenac 0.1%) was 2.57 ± 0.67 while in Group-B (ketorolac 0.4% treated arm) was 3.20 ± 0.61.Conclusion:Topical diclofenac 0.1% is statistically comparable to topical ketorolac 0.5% in precluding severity of pain after corneal collagen cross linkage operation.

Theoretical Studies of the Spin Hamiltonian Parameters and Local Distortions for Cu2+ in Alkaline Earth Lead Zinc Phosphate Glasses

Abstract The spin Hamiltonian parameters and local structures are theoretically studied for Cu2+-doped alkaline earth lead zinc phosphate (RPPZ, R=Mg, Ca, Sr, and Ba) glasses based on the high-order perturbation calculations for a tetragonally elongated octahedral 3d9 cluster. The relative elongation ratios are found to be ρ≈3.2%, 4.4%, 4.6%, and 3.3% for R=Mg, Ca, Sr, and Ba, respectively, because of the Jahn-Teller effect. The whole decreasing crystal-field strength Dq and orbital reduction factor k from Mg to Sr are ascribed to the weakening electrostatic coulombic interactions and the increasing probability of productivity of nonbridge oxygen (and hence increasing Cu2+–O2− electron cloud admixtures) under PbO addition, respectively, with increasing alkali earth ionic radius. The anomalies (the largest Dq and the next highest k among the systems) for R=Ba are attributed to the cross linkage of this large cation in the network. The overall increasing order (Mg≤Ba&lt;Ca&lt;Sr) of ρ is largely due to the decreasing crystal-field strength Dq and hence the decreasing force constant of the Cu2+–O2− bonds. The present studies would be helpful to understand local structures and the influences on the optical properties of RPPZ glasses containing copper dopants.

Construction of the di(trimethylolpropane) cross linkage and the phenylnaphthalene structure coupled with selective β-O-4 bond cleavage for synthesizing lignin-based epoxy resins with a controlled glass transition temperature

Lignin-based epoxy resins with controlled thermodynamic properties were synthesized.

Voltammetric Determination of Pindolol in Biological Fluids Using Molecularly Imprinted Polymer Based Biomimetic Sensor

A sensitive and selective electrochemical sensor for pindolol (PDL) was fabricated by embedding molecularly imprinted polymer (MIP) in graphite carbon paste. PDL imprinted polymer was prepared by free radical polymerization of itaconic acid (IA) and subsequent cross linkage with ethylene glycol dimethacrylate in the presence of PDL. The prepared MIP was subjected to extraction of template and then carbon paste electrode (CPE) was prepared by mixing optimized quantities of graphite, MIP and eicosane. The electrochemical behavior of PDL at MIP and non-imprinted polymer (NIP) modified CPEs have been investigated employing cyclic voltammetry (CV), and adsorptive stripping differential pulse voltammetry (AdSDPV). Chronocoulometry (CC) was used to approximate the surface coverage of analyte molecules which are specifically bound to MIP-CPE. Under the optimal experimental conditions, the sensor displayed linear relationship between the peak current and concentration of the PDL ranging from 0.1 μM to 50 μM, with the detection limit of 0.05 μM (S/N = 3). The presence of most common interferents and other structural analogues of PDL have no deleterious effect on the PDL anodic peak current. The fabricated sensor was successfully applied for the determination of PDL in serum and urine samples with recoveries in between 97 and 105%.

Influence of high-molecular-weight glutenin subunit composition at Glu-B1 locus on secondary and micro structures of gluten in wheat (Triticum aestivum L.)

Glutenin is one of the critical gluten proteins that affect the processing quality of wheat dough. High-molecular-weight glutenin subunits (HMW-GS) affect rheological behavior of wheat dough. This research demonstrated the effects of four variations of HMW-GS composition at the Glu-B1 locus on secondary and micro structures of gluten and rheological properties of wheat dough, using the bread wheat Xinong 1330 and its three near-isogenic lines (NILs). Results indicated that the Amide I bands of the four wheat lines shifted slightly, but the secondary structure, such as content of α-helices, β-sheets, disulfide bands, tryptophan bands and tyrosine bands, differed significantly among the four NILs. The micro structure of gluten in NIL 2 (Bx14+By15) and NIL 3 (Bx17+By18) showed more cross linkage, with two contrasting patterns. Correlation analysis demonstrated that the content of β-sheets and disulfide bonds has a significant relationship with dough stability, which suggests that the secondary structures could be used as predictors of wheat quality.

Self-Management of Anticoagulant Therapy in Mechanical Heart Valve Patients: A Matched Cohort Study

Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists for mechanical heart valves has demonstrated efficacy in randomized controlled trials. However, the effectiveness of PSM in clinical practice has only been investigated in small trials. Our aim was to evaluate the effectiveness of PSM of oral anticoagulant therapy in mechanical heart valve patients. We conducted a matched cohort study: cases were patients with a mechanical heart valve performing PSM affiliated with Aarhus University Hospital or Aalborg University Hospital, Denmark, in the period 1996 to 2012 (n = 615). Prospectively registered patient data were obtained from databases at two hospitals, and cross linkage between these databases and national patient registries provided detailed information on comorbidities and events. Control patients were matched (on sex, date of birth, year of first valve surgery, and grouped valve position) in a ratio of 5:1 (n = 3,075) with patients receiving conventional management who were randomly selected within the match group. The effectiveness and safety was estimated using major bleeding and thromboembolic events and death as outcomes. We observed low event rates in the PSM group. After 5 years, PSM was associated with a lower risk of all-cause mortality compared with conventional management (adjusted hazard ratio of 0.49, 95% confidence interval: 0.34 to 0.71). The hazard ratios for thromboembolism and major bleeding were 0.91 (95% confidence interval: 0.66 to 1.24) and 0.83 (95% confidence interval: 0.56 to 1.22). Owing to superior clinical effectiveness, self-managed oral anticoagulant therapy may potentially improve the standard of care for patients with mechanical heart valves.

Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy.

We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH–NH2–ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH–NH2–ICG and single layer chitosan-coated LDH–NH2–ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy.

A gelatin based antioxidant enriched biomaterial by grafting and saturation: Towards sustained drug delivery from antioxidant matrix

Proteins grafted with antioxidant molecules have drawn much attention due to their increased life time and biocompatibility. When protein macromolecules are cross linked chemically and physically with antioxidant molecules, they can act as antioxidant biomaterials as well as scaffolds to release the antioxidant molecules by diffusion. In our work, we have attempted to release catechin molecules from the matrix of glutathione grafted gelatin. Conjugation of glutathione and cross linkage was done by carbodiimide method to achieve smaller pores in the gelatin matrix and the characterization was performed by means of FTIR-ATR and calorimetric analyses. The glutathione grafted gelatin (GGSH) has been shown to have more thermal stability and pores with lesser radii than blank gelatin (bGEL). Free radical scavenging activity of GGSH was also found to be more than that of bGEL. Catechin was added to GGSH and bGEL by physical blending in order to achieve short term release of antioxidant molecules. CD spectra revealed that significant conformational changes occurred in secondary structure of gelatin upon interaction with catechin. Slower rate of catechin release from GGSH reflected the influence of cross linkage and physical interactive forces on the drug release properties. We conclude that the mixture of catechin with GGSH can be a potent antioxidant biomaterial releasing catechin at slower rate than the mixture of catechin with bGEL.

Influence of three alkalizing agents on some functional properties of cassava starch modified using epichlorohydrin

Influence of three alkalizing agents namely, potassium hydroxide (KOH) , ammonium hydroxide (NH4OH), and dimethyl sulphoxide (DMSO) during modification as modification facilitator on some functional properties of cassava starch modified using epichlorohydrin (EPI) at room temperature was studied. Assessment of the principal functional property; pasting properties and associated pasting indices of technological importance, notably peak viscosity and set back viscosity. The low peak viscosity (RVU) of the cassava EPI-modified starch ranged from 119.67-178.17; 128.50-161.17 for samples alkalized using KOH and DMSO respectively in comparison to the high peak viscosity (RVU) of the native starch. NH4OH was less effective alkalizing agent under the conditions used in this study. Cassava- EPI modified starch showed improved paste stability expressed in breakdown viscosity (RVU) values of 22.08-48.75 and 37.92-55.58 for KOH and DMSO alkalized samples respectively. Evaluation of other functional properties such as swelling power, apparent viscosity and paste clarity of the cassava-EPI modified starch showed alkaline-type dependent cross linkage activity of EPI. Assessment of all the functional properties of starch accomplished under the conditions employed in this study revealed that irrespective of concentration of EPI added, activity of alkalizing reagents is in the order: KOH&gt;DMSO&gt;NH4OH. DOI: http://dx.doi.org/10.3329/bjsir.v49i2.21997 Bangladesh J. Sci. Ind. Res. 49(2), 63-68, 2014

Protein Glycation: A Firm Link to Cause Metabolic Disease and their Complications

Glycation of proteins starts with the formation of Schiff base, followed by intermolecular rearrangement and conversion into Amadori products. When large amounts of Amadori products are formed, they undergo cross linkage to form a heterogeneous group of protein-bound moieties, termed as Advanced Glycation End products (AGEs). The formation of AGEs is irreversible process, causing structural and functional changes in protein. This results in generation of free radicals which play an important role in pathophysiology of ageing and diabetes. The rates of these reactions are quite slow and proteins with large amounts of lysine residues undergo glycation with significant amounts of AGEs. The unwanted consequences of protein glycation may lead to several metabolic disorders like diabetes, arteriosclerosis, osteoporosis and Alzheimer’s disease etc. and their complications. This commentary reviews the glycation of proteins which have already been demonstrated by us and others.

Modifying emission of ZnO nanoparticles in ZnO interceded polymer based hierarchical ordered nanocapsules

Here we report that a cationic polyamine in the presence of hydrogen phosphate spontaneously self-assemble due to ionic cross linkage to form aggregates, and when ~14nm ZnO is added in alkaline environment ZnO mediated hierarchical ordered nanocapsules are formed. These nanocapsules are of 200–500nm with a hydrodynamic radius of 170nm. Such nanocapsules alter the photoluminescence of ZnO nanoparticles. The photoluminescence properties of the ZnO based nanocapsules depend on excitation wavelengths. The visible emission of ZnO nanocapsules is due to the defects or vacancies that are located mainly on the nanoparticle surfaces during the interaction between polymer and ZnO in the nanocapsules. The relative photoluminescence quenching in ZnO nanocapsules compared to ZnO in polymer solution could be referred to aggregation of ZnO nanoparticles during nanocapsule formation.

The Synthesis of Diaminoanthraquinone Coloured Cross Linked Epoxy Resins and Their Application in Paint and Selected Polymers

Novel polymeric pigments were synthesized in xylene by cross linked epoxy resin with 1,4 and 1,5-diaminoanthraquinones, by varying weight fractions from 5% to 20% of the diaminoanthraquinone derivatives. FTIR, UV and solubility tests were carried out. The pigments were then used to colour PLA, PMMA, PE and also in emulsion paints using polyvinyl alcohol as binder. Their light fastness, surface drying time and surface hardening time were assessed. It was found that λmax of the 1,4-diaminoanthraquinone shifted towards longer wavelength after the cross linkage, in contrast to the 1,5-diaminoanthraquinone which suffered a blue shift. However in all the cases, the λmax was not affected by the weight fractions of the anthraquinones, but the absorptivity coefficients was significantly increased as the weight fractions of the anthraquinones increased. The light fastness properties of the coloured plastics varied from 4 to 7, indicating a trend of increase with the weight fractions of the anthraquinones. Similar observations were seen with the emulsion paints produced. In all the cases, the 1,4-diaminoanthraqunione produced better result.