A 13C NMR study of the role of plasticizers in the conduction mechanism of solid polymer electrolytes

The addition of low molecular weight solvents such as dimethyl formamide (DMF) and propylene carbonate (PC) to urethane crosslinked polyethers results in enhancement of polymer segmental motion, as determined in this work from polymer ¹³C spin lattice relaxation measurements (T₁) and glass transition temperatures. The formation of salt-polyether complexes results in a decrease in T₁, even in the presence of the plasticizer, indicating that the polymer ether molecules are still involved in the alkali metal coordination. In a polymer electrolyte containing 1 mol kg⁻¹ LiClO₄ the addition of DMF and PC have significantly different affects on the polymer mobility, although they both enhance the conductivity. The conductivity enhancement therefore is not solely the result of an increased solvent mobility.

Composition effects in polyetherurethane-based solid polymer electrolytes

Nuclear magnetic resonance spectroscopy (n.m.r.), dynamic mechanical thermal analysis (d.m.t.a.) and AC impedance techniques have been used in combination to probe the effect of electrolyte composition in an archetypal solid polymer electrolyte (SPE). A series of solid polymer electrolytes (SPEs) based on a urethane-crosslinked trifunctional poly(ethylene glycol) polymer host containing dissolved ionic species (LiClO₄ and LiCF₃SO₃) have been studied. D.m.t.a. has established that increasing LiClO₄ concentration causes a decrease in the polymer segmental mobility, owing to the formation of transient crosslinks via cation-polymer interaction. Investigation of the distribution of mechanical/structural relaxation times for the LiClO₄/polymer complex with d.m.t.a. reveals that increasing LiClO₄ concentration causes a slight broadening of the distribution, indicating a more heterogeneous environment. Results of n.m.r. ⁷Li T₁ and T₂ relaxation experiments support the idea that higher salt concentrations encourage ionic aggregation. This is of critical importance in determining the conductivity of the material since it affects the number of charge carriers available. Introduction of the plasticiser tetraglyme into the LiClO₄-based SPEs suppresses the glass transition temperature of the SPE, and causes a significant broadening of the relaxation time distribution (as measured by d.m.t.a.).

Mechanical properties of polyether-plasticiser-salt systems as polymer electrolytes

The mechanical properties of urethane crosslinked poly(ethylene oxide-co-propylene oxide) glyceryl ether-plasticiser (tetraethylene glycol dimethyl ether, or methylformamide)-salt (LiClO₄)-based polymer electrolytes have been studied. It was found that, with increasing concentration of salt, the elastic modulus and tensile strength of the materials unexpectedly decrease. This is interpreted in terms of a predominance of intramolecular coordination of the Li⁺ ions by the polymer.

A novel nanoplatform for oral delivery of anti-cancer biomacromolecules

Oral administration of bio–macromolecules is an uphill task and the challenges from varying pH and enzymatic activity are difficult to overcome. In this regard, nanotechnology promises the new hope and offers advantages such as controlled release, target specific delivery, combinatorial therapy and many more. In this study, we demonstrate the formulation of a novel alginate enclosed, chitosan coated ceramic, anti cancer nano carrier (ACSC NC). These NC were loaded with multi functional anti cancer bovine lactoferrin (Lf), a natural milk based protein, for improvement of intestinal absorption, in order to develop a novel platform to carry anti cancer protein and/or peptides for oral therapy. Here we demonstrate the size, morphology, internalisation and release profiles of the nanoparticles (NC) under varying pH as perceived in human digestive system. We further determine the uptake of these particles by colon cancer cell lines by measuring the endocytosis and transcytosis of the NC. These NC can be used for future targeted protein/peptide or nucleic acid based drug delivery to treat difficult diseases including cancer.

Short-term bone biochemical response to a single bout of high-impact exercise

Bone response to a single bout of exercise can be observed with biochemical markers of bone formation and resorption. The purpose of this study was to examine the response of bone biochemical markers to a single bout of exhaustive high-impact exercise. 15 physically active young subjects volunteered to participate. The subjects performed continuous bilateral jumping with the ankle plantarflexors at 65 % of maximal ground reaction force (GRF) until exhaustion. Loading was characterized by analyzing the GRF recorded for the duration of the exercise. Venous blood samples were taken at baseline, immediately after, 2h and on day 1 and day 2 after the exercise. Procollagen type I amino terminal propeptide (P1NP, marker of bone formation) and carboxyterminal crosslinked telopeptide (CTx, marker of bone resorption) were analyzed from the blood samples. CTx increased significantly (32 %, p = 0.015) two days after the exercise and there was a tendensy towards increase seen in P1NP (p = 0.053) one day after the exercise. A significant positive correlation (r = 0.49 to 0.69, p ≤ 0.038) was observed between change in P1NP from baseline to day 1 and exercise variables (maximal slope of acceleration, body weight (BW) adjusted maximal GRF, BW adjusted GRF exercise intensity and osteogenic index). Based on the two biochemical bone turnover markers, it can be concluded that bone turnover is increased in response to a very

A new way to nanostructure hydrogels : electrospun thermo-responsive islands-in-the-sea nanofibres

Islands-in-the-sea nanofibres are a very interesting system: one polymer (islands) is distributed in fibrillar domains within a second polymer (sea). This fibre geometry is often used in microfiber technologies to obtain very fine fibers, by removing the “sea” polymer. This geometry also allows to combine two polymers with very different properties. In this work this geometry is introduced applied to electrospun hydrogel nanofibers, in a novel fashion, and as a way to improve and stabilize the hydrogel nanofibers. Thermo-responsive islands-in-the-sea nanofibers are here produced by electrospinning solutions of a hydrogel-forming thermo-responsive polymer (crosslinked poly(N-isopropylacrylamide), PNIPAM) and a reinforcing polymer (polyetherketone cardo, PEK-c). The two polymers are thermodynamically incompatible in solution and phase separation takes place, which allows the instant formation of islands-in-the-sea nanofibers upon electrospinning. PNIPAM was then crosslinked post-spinning using an oligomeric silsesquioxane. The formed nanocomposite nanofibers showed intrinsic nanostructure, where the fibril-like PNIPAM domains are intimately adjacent to the strong PEK-c domains. Upon contacting with water, the hydrogel domains became instantly highly swollen, while the PEK-c domains did not. As a result, very wrinkly, swollen fibers were obtained, with increased capillary action, as demonstrated through confocal microscopy. The composite nanofibers in water showed excellent swelling ratios and very fast responses to temperature variations (of the order of 1 second) with morphological and optical effects: variations in fiber-diameter were accompanied by optical transitions: transparent-opaque. The produced hydrogel nanofibers also presented improved mechanical properties (even with small amounts of PEK-c), when compared to their crosslinked-PNIPAM-only nanofibers. It will be also shown how these materials can be used as optical actuators and smart hydrogel platforms with tuneable contact angle and morphology. In brief, this work aims to demonstrate a new platform technology which can be applied to several hydrogel systems, to achieve hydrogel-based composites with new and improved properties, while retaining (and improving) the main properties of the hydrogel. Here this was demonstrated by showing that the composite materials showed thermo-responsiveness, and enhanced transition kinetics.

Novel alginate-enclosed chitosan–calcium phosphate-loaded iron-saturated bovine lactoferrin nanocarriers for oral delivery in colon cancer therapy

Aim: To develop polymeric-ceramic nanocarriers (NCs) in order to achieve oral delivery of the anticancer neutraceutical iron-saturated bovine lactoferrin (Fe-bLf) protein.

Materials & methods: Fe-bLf or paclitaxel (Taxol®) were adsorbed onto calcium phosphate nanocores, enclosed in biodegradable polymers chitosan and alginate. The Fe-bLf or Taxol-loaded NCs indicated as AEC–CP–Fe-bLf or AEC–CP–Taxol NCs, respectively, were made by combination of ionic gelation and nanoprecipitation. Size distribution, morphology, internalization and release profiles of the NCs were studied along with evaluation of in vitro and in vivo anticancer activities and compared with paclitaxel.

Results: AEC–CP–Fe-bLf NCs obtained spherical morphology and showed enhanced endocytosis, transcytosis and anticancer activity in Caco-2 cells in vitro. AEC–CP–Fe-bLf NCs were supplemented in an AIN 93G diet and fed to mice in both prevention and treatment human xenograft colon cancer models. AEC–CP–Fe-bLf NCs were found to be highly significantly effective when given orally, as a pretreatment, 1 week before Caco-2 cell injections. None of the mice from the AEC–CP–Fe-bLf NC-fed group developed tumors or showed any signs of toxicity, while the mice fed the control AIN 93G diet showed normal tumor growth. Fe-bLf or Taxol, when given orally in a diet as nanoformulations post-tumor development, showed a significant regression in the tumor size with complete inhibition of tumor growth later, while intratumoral injection of Taxol just delayed the growth of tumors. The pharmacokinetic and bioavailability studies indicated that nanoformulated Fe-bLf was predominantly present on tumor cells compared to non-nanoformulated Fe-bLf. Fe-bLf-loaded NCs were found to help in absorption of iron and thus may have utility in enhancing the iron uptake during iron deficiency without interfering with the absorption of calcium.

Conclusion: With the promising results of our study, the future potential of NC-loaded Fe-bLf in chemoprevention and in the treatment of human colon cancer, deserves further investigation for translational research and preclinical studies of other malignancies.

Mechanical Reinforcement of Continuous Flow Spun Polyelectrolyte Complex Fibers

A simple continuous flow wet-spinning method to achieve mechanical reinforcement of the two oppositely charged biopolymers chitosan and gellan gum is described. The mechanical properties of these biopolymers are influenced by the order of addition. Using a facile method for mechanical reinforcement of gellan gum/chitosan fibers resulted in increases in Young's modulus, tensile strength, and toughness. Spinning gellan gum into chitosan resulted in the strongest fibers. We show that our fibers can provide a mechanical alternative for bio-fibers without the need of cross-linking. It is demonstrated that the fibers become ionically conducting in the presence of water vapor.

Carbon Nanotube Biofiber Formation in a Polymer-Free Coagulation Bath

A novel solution spinning method to produce highly conducting carbon nanotube (CNT) biofibers is reported. In this process, carbon nanotubes are dispersed using biomolecules such as hyaluronic acid, chitosan, and DNA, and these dispersions are used as spinning solutions. Unlike previous reports in which a polymer binder is used in the coagulation bath, these dispersions can be converted into fibers simply by altering the nature of the coagulation bath via pH control, use of a crosslinking agent, or use of a biomolecule-precipitating solvent system. With strength comparable to most reported CNT fibers to date, these CNT biofibers demonstrate superior electrical conductivities. Cell culture experiments are performed to investigate the cytotoxicity of these fibers. This novel fiber spinning approach could simplify methodologies for creating electrically conducting and biocompatible platforms for a variety of biomedical applications, particularly in those systems where the application of an electrical field is advantageous?for example, in directed nerve and/or muscle repair.

Anti-microbial activities of novel nanoformulated lactoferrin through oral administration

A biomolecular delivery system consisting of a novel alginate enclosed, chitosan coated ceramic antimicrobial nanocarrier containing lactoferrin (AEC-CP-Fe-bLf) and development of this multifunctional bovine iron saturated lactoferrin nanotechnology based drug delivery systems for finding treatment to parasitic and bacterial diseases was prepared. Since lactoferrin is a naturally occurring molecule its clinical application would be welcome.

Integrated DNA extraction and amplification using electrokinetic pumping in a microfluidic device

An integrated system employing anion exchange for the extraction of DNA from biological samples prior to polymerase chain reaction DNA amplification has been developed, based on microfluidic methodology utilising electrokinetic pumping. In this system, the biological samples were added directly to chitosan-coated silica beads to facilitate DNA immobilisation. The purified, pre-concentrated DNA was then eluted using a combination of electro-osmotic flow enhanced with electrophoretic mobility, which enable DNA to be transported by both mechanisms into the DNA amplification chamber. Through optimisation of the DNA elution conditions, average DNA extraction efficiencies of 69.1% were achievable. Subsequent DNA amplification performed on the microfluidic system demonstrated not only the ability to use electrokinetic movement to integrate the two processes on a single device, but also that the quality and quantity of DNA eluted was suitable for downstream analysis. This work offers an attractive real-world to chip interface and a route to simpler Lab-on-a-Chip technology which eliminates the need for moving parts.

Ultrafine PDMS fibers: Preparation from in situ curing-electrospinning and mechanical characterization

Polydimethylsiloxane (PDMS) fibers with unexpected elasticity were prepared by a modified core-shell electrospinning method using a commercially-available liquid PDMS precursor (Sylgard 184) and polyvinylpyrrolidone (PVP) as core and sheath materials, respectively. The liquid PDMS precursor was crosslinked in situ to form a solid core when the newly-electrospun core-sheath nanofibers were deposited onto a hot-plate electrode collector. After dissolving the PVP sheath layer off the fibers, net PDMS fibers showed larger average diameter than core-sheath fibers, with an average diameter around 1.35 μm. The tensile properties of both single fibers and fibrous mats were measured. Single PDMS fibers had a tensile strength and elongation at break of 6.0 MPa and 212%, respectively, which were higher than those of PDMS cast film (4.9 MPa, 93%). The PDMS fiber mat had larger elongation at break than the single PDMS fibers, which can be drawn up to 403% their original length. Cyclic loading tests indicated a Mullin effect on the PDMS fiber mats. Such a superior elastic feature was attributed to the PDMS molecular orientation within fibers and the randomly-orientated fibrous structure. Highly-elastic, ultrafine PDMS fibers may find applications in strain sensors, biomedical engineering, wound healing, filtration, catalysis, and functional textiles. © The Royal Society of Chemistry 2014.

Fe-bLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc

To validate the anticancer efficacy of alginate-enclosed, chitosan-conjugated, calcium phosphate, iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (NCs) with improved sustained release and ability to induce apoptosis by downregulating survivin, as well as cancer stem cells.

Optimisation of the microencapsulation of tuna oil in gelatin-sodium hexametaphosphate using complex coacervation.

The microencapsulation of tuna oil in gelatin-sodium hexametaphosphate (SHMP) using complex coacervation was optimised for the stabilisation of omega-3 oils, for use as a functional food ingredient. Firstly, oil stability was optimised by comparing the accelerated stability of tuna oil in the presence of various commercial antioxidants, using a Rancimat™. Then zeta-potential (mV), turbidity and coacervate yield (%) were measured and optimised for complex coacervation. The highest yield of complex coacervate was obtained at pH 4.7 and at a gelatin to SHMP ratio of 15:1. Multi-core microcapsules were formed when the mixed microencapsulation system was cooled to 5 °C at a rate of 12 °C/h. Crosslinking with transglutaminase followed by freeze drying resulted in a dried powder with an encapsulation efficiency of 99.82% and a payload of 52.56%. Some 98.56% of the oil was successfully microencapsulated and accelerated stability using a Rancimat™ showed stability more than double that of non-encapsulated oil.