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Lai S.-M.,National Ilan University | Chen W.-C.,Chinese Culture University | Wu T.-W.,Chinese Culture University | Yang A.J.-M.,Industrial Science and Technology Network Inc. | Yang C.-H.,Chinese Culture University
Journal of Macromolecular Science, Part B: Physics | Year: 2011

Chitosan/modified silica nanocomposites, with a sol-gel process being used to prepare a silanol quaternary ammonium modified silica possessing antimicrobial activity, were investigated, as well as the thermal properties, morphology, optical, mechanical, antimicrobial, and adsorption properties of this type of nanocomposite. Grafting of the modifier onto nanosilica was confirmed through the Fourier transform infrared (FTIR) spectra. X-ray diffraction patterns indicated that the chitosan structure was not disrupted from the incorporation of the modified silica. Fracture surfaces with no clear micro-phase separation were observed by scanning electron microscopy (SEM), which indicated the good interaction of chitosan and the modified silica. The organic modifier tended to cause the aggregation of the modified silica at higher content on a submicron scale based on transmission electron microscopy (TEM) analysis, which might be due to a decrease of the stability factor originating from the negative charges on silica.With the introduction of modified silica, the optical transmittance decreased at higher organic modifier content in agreement with TEM analysis. The elongation at break remained largely unchanged, but tensile strength and Young's moduli deteriorated in modified silica filled systems in comparison with pure silica filled systems. The introduction of the organic modified silica gave a higher antibacterial activity. All nanocomposites were capable of chelating Cu (II) as well as Fe (III) at a different degree. Thus, the prepared chitosan/modified silica nanocomposites exhibited both antimicrobial and chelating properties. Copyright © Taylor & Francis Group, LLC.


David A.E.,University of Maryland University College | David A.E.,Industrial Science and Technology Network Inc. | Gong J.,University of Michigan | Chertok B.,University of Michigan | And 7 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2012

Macromolecules present a remarkable potential as future therapeutics. However, their translation into clinical practice has been hampered by an inherently low bioavailability. Cell-penetrating peptides (CPP) have been recently shown to significantly improve on the bioavailability of macromolecules. Yet, the high cost associated with development and production of these peptides is a major factor hindering their rapid deployment beyond the laboratory. Here, we describe a facile and robust methodology for efficient and large-scale production of low-molecular-weight protamine-a potent CPP of great clinical potential. Our methodology is based on the immobilization of thermolysin, an enzyme catalyzing digestion of native protamine, on chemically surface-modified gels produced by silica sol-gel chemistry. Thermolysin was immobilized at extremely high matrix loading of 733 mg/g matrix and exhibited good thermal and pH stability, indicating robustness with respect to processing conditions. The mechanical properties of the silica matrix further allowed utilization of the immobilized thermolysin in both batch and packed-bed reactor systems to produce the LMWP peptide in high yields. Results presented here are of high significance as this efficient and cost-effective production of high purity LMWP could enable clinical translation of many potential macromolecular drugs. Copyright © 2011 Wiley Periodicals, Inc.


Cole A.J.,University of Michigan | David A.E.,University of Michigan | David A.E.,Industrial Science and Technology Network Inc. | Wang J.,University of Michigan | And 5 more authors.
Biomaterials | Year: 2011

While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, potentially enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37 °C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC0-∞. Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that a polyethylene glycol modified, cross-linked starch-coated MNP is a promising platform for enhanced magnetic tumor targeting, warranting further study in tumor models. © 2010 Elsevier Ltd.


Chertok B.,University of Michigan | Chertok B.,Massachusetts Institute of Technology | Cole A.J.,University of Michigan | David A.E.,University of Michigan | And 3 more authors.
Molecular Pharmaceutics | Year: 2010

Magnetic nanoparticles (MNP) have been widely studied for use in targeted drug delivery. Analysis of MNP biodistribution is essential to evaluating the success of targeting strategies and the potential for off-target toxicity. This work compared the applicability of inductively coupled plasma optical emission spectroscopy (ICP-OES) and electron spin resonance (ESR) spectroscopy in assessing MNP biodistribution. Biodistribution was evaluated in 9L-glioma bearing rats administered with MNP (12-25 mg Fe/kg) under magnetic targeting. Ex vivo analysis of MNP in animal tissues was performed with both ICP-OES and ESR. A cryogenic method was developed to overcome the technical hurdle of loading tissue samples into ESR tubes. Comparison of results from the ICP-OES and ESR measurements revealed two distinct relationships for organs accumulating high or low levels of MNP. In organs with high MNP accumulation such as the liver and spleen, data were strongly correlated (r = 0.97, 0.94 for the liver and spleen, respectively), thus validating the equivalency of the two methods in this high concentration range (>1000 nmol Fe/g tissue). The two sets of measurements, however, differed significantly in organs with lower levels of MNP accumulation such as the brain, kidney, and the tumor. Whereas ESR resolved MNP to 10-55 nmol Fe/g tissue, ICP-OES failed to detect MNP because of masking by endogenous iron. These findings suggest that ESR coupled to cryogenic sample handling is more robust than ICP-OES, attaining better sensitivity in analyses. Such advantages render ESR the method of choice for accurate profiling of MNP biodistribution across tissues with high variability in nanoparticle accumulation. © 2009 American Chemical Society.


Cole A.J.,University of Michigan | David A.E.,University of Michigan | David A.E.,Industrial Science and Technology Network Inc. | Wang J.,University of Michigan | And 4 more authors.
Biomaterials | Year: 2011

Magnetic iron oxide nanoparticles (MNPs) have been studied to circumvent the limitations of status-quo brain tumor therapy and can be targeted by applying an external magnetic field to lesions. To address the pharmacokinetic shortcomings of MNPs that can limit targeting efficiency, we recently reported a long-circulating polyethylene glycol modified, cross-linked starch MNP (PEG-MNP) suitable for magnetic targeting. Using a rat model, this work explores the biodistribution patterns of PEG-MNPs in organs of elimination (liver, spleen, lung, and kidney) and shows proof-of-concept that enhanced magnetic brain tumor targeting can be achieved due to the relatively long circulation lifetime of the nanoparticles. Reductions in liver (∼12-fold) and spleen (∼2.5-fold) PEG-MNP concentrations at 1. h compared to parent starch-coated MNPs (D) confirm plasma pharmacokinetics observed previously. While liver concentrations of PEG-MNPs remained considerably lower than those observed for D at 1. h through 60 h, spleen values continue to increase and are markedly higher at later time points - a trend also observed with histology. Limited to no distribution of PEG-MNPs was visualized in lung or kidney throughout the 60. h course evaluated. Enhanced, selective magnetic brain tumor targeting (t = 1 h) of PEG-MNPs (12 mg Fe/kg) was confirmed in 9L-glioma tumors, with up to 1.0% injected dose/g tissue nanoparticle delivery achieved - a 15-fold improvement over targeted D (0.07% injected dose/g tissue). MRI and histological analyses visually confirmed enhanced targeting and also suggest a limited contribution of passive mechanisms to tissue retention of nanoparticles. Our results are exciting and justify both further development of PEG-MNP as a drug delivery platform and concurrent optimization of the magnetic brain tumor targeting strategy utilized. © 2011 Elsevier Ltd.


Cole A.J.,University of Michigan | Yang V.C.,University of Michigan | Yang V.C.,Tianjin Medical University | David A.E.,University of Michigan | David A.E.,Industrial Science and Technology Network Inc.
Trends in Biotechnology | Year: 2011

Interest in utilizing magnetic nanoparticles (MNP) for biomedical applications has increased considerably over the past two decades. This excitement has been driven in large part by the success of MNPs as contrast agents in magnetic resonance imaging. The recent investigative trend with respect to cancer has continued down a diagnostic path, but has also turned toward concurrent therapy, giving rise to the distinction of MNPs as potential " theranostics" Here we review both the key technical principles of MNPs and ongoing advancement toward a cancer theranostic MNP. Recent progress in diagnostics, hyperthermia treatments, and drug delivery are all considered. We conclude by identifying current barriers to clinical translation of MNPs and offer considerations for their future development. © 2011 Elsevier Ltd.


Patent
Industrial Science and Technology Network Inc. | Date: 2014-07-21

This invention relates to the field of thermal insulation. In particular, the invention describes superinsulation articles having a desired porosity, reduced pore size and cost-effective methods for manufacturing such articles. In one aspect of the present invention, the article may comprise a material system with at least about 20% porosity. In a further aspect of the invention, an article may comprise greater than about 25% of nanopores having a pore size no greater than about 1500 nanometers in its shortest axis.


Trademark
Industrial Science and Technology Network Inc. | Date: 2012-03-05

Adhesive plastic film for industrial and commercial use; Laminated plastic films for use on windows; Plastic film for commercial and industrial use; Semi-finished plastic film coated and chemically treated to have specific optical properties, namely, anti-fog, anti-reflection and antistain for use in home and auto windows.


Patent
Industrial Science and Technology Network Inc. | Date: 2014-04-18

A foam extrusion slot die is provided, comprising a plurality of parallel dividers extending transversely across the slot, wherein the plurality of dividers define a plurality of adjacent rectangular slit openings, each having a length extending perpendicularly across the lateral length of the slot die. An article of manufacture is provided, comprising a polymer material system with at least 95% porosity comprising greater than 10%>asymmetrical pores. A method for an article of manufacture is provided comprising: extruding polymer material through an extruder die opening having an output orifice partitioned by a plurality of parallel dividers defining a plurality of adjacent slit openings each having a vertical height greater than a lateral width.

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