Release of proteins via ion exchange from albumin-heparin microspheres

Albumin-heparin and albumin microspheres were prepared as ion exchange gels for the controlled release of positively charged polypeptides and proteins. The adsorption isotherms of chicken egg and human lysozyme, as model proteins, on microspheres were obtained. An adsorption isotherm of chicken egg lysozyme on albumin-heparin microspheres was linear until saturation was abruptly reached,\ud \ud The adsorption isotherms of human lysozyme at low and high ionic strength were typical of adsorption isotherms of proteins on ion exchange gels. The adsorption of human lysozyme on albumin-heparin and albumin microspheres fit the Freundlich equation suggesting heterogeneous binding sites. This was consistent with the proposed multivalent, electrostatic interactions between human lysozyme and negatively charged microspheres. Scatchard plots of the adsorption processes of human lysozyme on albumin-heparin and albumin microspheres suggested negative cooperativity, while positive cooperativity was observed for chicken egg lysozyme adsorption on albumin-heparin microspheres.\ud \ud Human lysozyme loading of albumin-heparin microspheres was 3 times higher than with albumin microspheres, with long term release occurring via an ion exchange mechanism. Apparent diffusion coefficients of 2.1 × 10-1 and 3.9 × 10-11cm2/sec were obtained for the release of human lysozyme from albumin-heparin and albumin microspheres, respectively. The release was found to be independent of diffusion, since the rate determining step was likely an adsorption/desorption processes. An apparent diffusion coefficient of 4.1 × 10-12 cm2/sec was determined for the release of chicken egg lysozyme from albumin-heparin microspheres.\ud \ud Low release of the lysozymes from albumin-heparin microspheres was observed in deionized water, consistent with the proposed ion exchange release mechanism. Overall, albumin-heparin microspheres demonstrated enhanced ion exchange characteristics over albumin microspheres

Microstructure of metal matrix composites reinforced by ceramic microballoons

Metal matrix composites reinforced by ceramic hollow microspheres were produced as special porous metals, called metal matrix syntactic foams (MMSFs). In this paper the microstructure of the ceramic hollow microspheres as reinforcing element was investigated in connection with the production of MMSFs by pressure infiltration. SL150 and SL300 type ceramic microspheres from Envirospheres Ltd. (Australia) were investigated. They contained various oxide ceramics, mainly Al2O3 and SiO2. The chemical composition and the microstructure of the microspheres had strong effect on their infiltration characteristics; therefore in the view of MMSF production it was very important to know microstructural details about the microspheres. Due to this energy dispersive X-ray spectroscopy maps were recorded from the cross sections of the microspheres’ wall. The results showed that the Al2O3 and SiO2 distribution was not equal; the Al2O3 phase was embedded in the surrounding mullite and SiO2 phase in the form of needles. Line energy dispersive X-ray spectroscopy measurements were performed in order to investigate the possible reaction between the different aluminium alloy matrices and the ceramic microspheres. The results showed that, due to the uneven distribution of Al2O3 rich particles, the molten aluminium could reduce the SiO2 rich parts of the microspheres and the wall of the hollow microspheres became damaged and degraded. This chemical reaction between the microspheres and the walls could make the infiltration easier, but the resulting mechanical properties will be lower due to the damaged microsphere walls

Slipping friction of an optically and magnetically manipulated microsphere rolling at a glass-water interface

The motion of submerged magnetic microspheres rolling at a glass-water interface has been studied using magnetic rotation and optical tweezers combined with bright-field microscopy particle tracking techniques. Individual microspheres of varying surface roughness were magnetically rotated both in and out of an optical trap to induce rolling, along either plain glass cover slides or glass cover slides functionalized with polyethylene glycol. It has been observed that the manipulated microspheres exhibited nonlinear dynamic rolling-while-slipping motion characterized by two motional regimes: At low rotational frequencies, the speed of microspheres free-rolling along the surface increased proportionately with magnetic rotation rate; however, a further increase in the rotation frequency beyond a certain threshold revealed a sharp transition to a motion in which the microspheres slipped with respect to the external magnetic field resulting in decreased rolling speeds. The effects of surface-microsphere interactions on the position of this threshold frequency are posed and investigated. Similar experiments with microspheres rolling while slipping in an optical trap showed congruent results.Comment: submitted to Journal of Applied Physics, 11 figure

Carbon nanotube decorated magnetic microspheres as an affinity matrix for biomolecules

Carbon nanotube (CNT) decorated magnetic microspheres were fabricated to develop a multimodal platform that utilizes non-covalent molecular interactions of CNTs to magnetically separate biomolecules. Hybrid CNT-microspheres prepared by a feasible method reported herein had a well-defined structure as characterized by Raman spectroscopy and scanning electron microscopy. Binding interactions of resulting magnetic CNT-microspheres with DNA oligonucleotides were studied to demonstrate that single stranded DNA (ssDNA) in a solution can be effectively recovered by magnetic CNT-microspheres through strong physical wrapping of DNA around CNTs' walls. The magnetic character of these CNT-microspheres combined with their capability to bind other molecules including DNA allows their use as an affinity matrix that can be utilized in affinity separation of biomolecules, and also as a platform to monitor non-covalent binding interactions of CNTs with other biomolecules. As a proof of concept, we report on the use of these CNT-microspheres in in vitro selection of ssDNA aptamers against carcinoembryonic antigen (CEA), a cancer biomarker, by Systematic Evolution of Ligands by Exponential Enrichment (SELEX). ssDNA aptamer candidates that have strong affinity towards CEA were successfully separated magnetically from a pool of ssDNA (1014 molecules). Our results demonstrate that CNT-microspheres can serve as strong tools for affinity separation methodologies and can be utilized for various affinity pairs in solution

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma

Spatiotemporal release of VEGF from biodegradable polylactic-co-glycolic acid microspheres induces angiogenesis in chick chorionic allantoic membrane assay

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.While vascular endothelial growth factor (VEGF) is an acknowledged potent pro-angiogenic agent there is a need to deliver it at an appropriate concentration for several days to achieve angiogenesis. The aim of this study was to produce microspheres of biodegradable polylactic-co-glycolic acid (PLGA) tailored to achieve sustained release of VEGF at an appropriate concentration over seven days, avoiding excessive unregulated release of VEGF that has been associated with the formation of leaky blood vessels. Several formulations were examined to produce microspheres loaded with both human serum albumin (HSA) and VEGF to achieve release of VEGF between 3 and 10 ng per ml for seven days to match the therapeutic window desired for angiogenesis. In vitro experiments showed an increase in endothelial cell proliferation in response to microspheres bearing VEGF. Similarly, when microspheres containing VEGF were added to the chorionic membrane of fertilised chicken eggs, there was an increase in the development of blood vessels over seven days in response, which was significant for microspheres bearing VEGF and HSA, but not VEGF alone. There was an increase in both blood vessel density and branching – both signs of proangiogenic activity. Further, there was clearly migration of cells to the VEGF loaded microspheres. In summary, we describe the development of an injectable delivery vehicle to achieve spatiotemporal release of physiologically relevant levels of VEGF for several days and demonstrate the angiogenic response to this. We propose that such a treatment vehicle would be suitable for the treatment of ischemic tissue or wounds

Electrospray synthesis of PLGA TIPS microspheres

We successfully demonstrate the synthesis of polymer microspheres using a single electrospray source, and show their physical characterisation. Electrospray has proven to be a versatile method to manufacture particles, giving tight control over size with quasi-monodisperse size distributions. It is a liquid atomisation technique that generates a monodisperse population of highly charged liquid droplets over a broad size range (nanometres to tens of microns). The droplets contain liquid precursors for the in-flight synthesis of particles, and control over the trajectory of these droplets can be precisely manipulated with the use of electric fields to drive them to a grounded substrate. This study reports a method to synthesize poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray and thermally induced phase separation (TIPS) techniques, followed by subsequent freeze-drying, for particle production. These microspheres are of interest as vehicles for controlled drug release systems