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Kang Liu,1 Weijuan Chen,2 Tingting Yang,1 Baofang Wen,1 Dejun Ding,1 Michael Keidar,3 Jinbao Tang,1 Weifen Zhang1 1College of Pharmacy, Weifang Medical University, Weifang, 2Department of Pathology, People’s Hospital of Shouguang, Shouguang, People’s Republic of China; 3Department of Mechanical and Aerospace Engineering, School of Engineering and Applied Science, The George Washington University, Washington, DC, USA Abstract: High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 µm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs. Keywords: paclitaxel, quercetin, oleic acid-conjugated chitosan, nanoparticles, polymeric microspheres, pulmonary delivery

Mian Wang,1 Benjamin M Geilich,2 Michael Keidar,3 Thomas J Webster1,4 1Department of Chemical Engineering, 2Department of Bioengineering, Northeastern University, Boston, MA, 3Department of Mechanical and Aerospace Engineering, George Washington University, Washington, DC, USA; 4Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT) is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX), an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP) was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed) at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed). With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed) compared to not using a light source (45% were killed) or using a UV light source (65% were killed). In summary, these results indicated for the first time that PpIX-loaded polymersomes together with CAP posttreatment could be a promising tool for skin cancer drug delivery with selective toxicity toward melanoma cells sparing healthy fibroblasts. Keywords: melanoma, polymersomes, protoporphyrin IX, cold atmospheric plasma, photodynamic therapy

Wei Zhu,1 George Teel,1 Christopher M O’Brien,1 Taisen Zhuang,1 Michael Keidar,1 Lijie Grace Zhang1–3 1Department of Mechanical and Aerospace Engineering, 2Department of Biomedical Engineering, 3Department of Medicine, The George Washington University, Washington, DC, USA Abstract: Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium’s osseointegration involves inducing biomimetic nanotopography to enhance cell–implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC) attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications. Keywords: titanium, mesenchymal stem cell, plasma, nanocoating, orthopedics

Owen Im1, Jian Li2, Mian Wang2, Lijie Grace Zhang2,3, Michael Keidar2,31Department of Biomedical Engineering, Duke University, Durham, NC; 2Department of Mechanical and Aerospace Engineering, 3Institute for Biomedical Engineering and Institute for Nanotechnology, The George Washington University, Washington, DC, USABackground: Many shortcomings exist in the traditional methods of treating bone defects, such as donor tissue shortages for autografts and disease transmission for allografts. The objective of this study was to design a novel three-dimensional nanostructured bone substitute based on magnetically synthesized single-walled carbon nanotubes (SWCNT), biomimetic hydrothermally treated nanocrystalline hydroxyapatite, and a biocompatible hydrogel (chitosan). Both nanocrystalline hydroxyapatite and SWCNT have a biomimetic nanostructure, excellent osteoconductivity, and high potential to improve the load-bearing capacity of hydrogels.Methods: Specifically, three-dimensional porous chitosan scaffolds with different concentrations of nanocrystalline hydroxyapatite and SWCNT were created to support the growth of human osteoblasts (bone-forming cells) using a lyophilization procedure. Two types of SWCNT were synthesized in an arc discharge with a magnetic field (B-SWCNT) and without a magnetic field (N-SWCNT) for improving bone regeneration.Results: Nanocomposites containing magnetically synthesized B-SWCNT had superior cytocompatibility properties when compared with nonmagnetically synthesized N-SWCNT. B-SWCNT have much smaller diameters and are twice as long as their nonmagnetically prepared counterparts, indicating that the dimensions of carbon nanotubes can have a substantial effect on osteoblast attachment.Conclusion: This study demonstrated that a chitosan nanocomposite with both B-SWCNT and 20% nanocrystalline hydroxyapatite could achieve a higher osteoblast density when compared with the other experimental groups, thus making this nanocomposite promising for further exploration for bone regeneration.Keywords: nanomaterials, single-walled carbon nanotube, nanocrystalline hydroxyapatite, chitosan, bone regeneration, biomimetic

Plasma transport in a hybrid dc vacuum is plasma source for ion deposition and plasma immersion treatment is considered. It is found that external crossed electric and magnetic fields near the substrate can significantly reduce the relative amplitude of ion current fluctuations I(sub f) at the substrate surface.

Low temperature plasmas have been used in various plasma processing applications for several decades. But it is only in the last thirty years or so that sources generating such plasmas at atmospheric pressure in reliable and stable ways have become more prevalent. First, in the late 1980s, the dielectric barrier discharge was used to generate relatively large volume diffuse plasmas at atmospheric pressure. Then, in the early 2000s, plasma jets that can launch cold plasma plumes in ambient air were developed. Extensive experimental and modeling work was carried out on both methods and much of the physics governing such sources was elucidated. Starting in the mid-1990s, low temperature plasma discharges have been used as sources of chemically reactive species that can be transported to interact with biological media, cells, and tissues and induce impactful biological effects. However, many of the biochemical pathways whereby plasma affects cells remain not well understood. This situation is changing rather quickly because the field, known today as "plasma medicine," has experienced exponential growth in the last few years thanks to a global research community that engaged in fundamental and applied research involving the use of cold plasma for the inactivation of bacteria, dental applications, wound healing, and the destruction of cancer cells/tumors. In this perspective, the authors first review the physics as well as the diagnostics of the principal plasma sources used in plasma medicine. Then, brief descriptions of their biomedical applications are presented. To conclude, the authors' personal assessment of the present status and future outlook of the field is given. [ABSTRACT FROM AUTHOR]

An analysis of the free, steady state, two-dimensional radial plasma flow initiated between a pair of disk-shaped electrodes of a hot anode vacuum arc in the hydrodynamic approximation was conducted. Experimental studies focused on velocity, radial spreading of the arc current and potential distribution and the impact of the self-magnetic field on the plasma density. Results demonstrate that the potential distribution is strongly nonsymmetric with respect to the central plane due to the influence of the plasma density gradients on the current spreading.

The effect of plasma and macroparticle (MP) transport in magnetized plasma guides as well as the plasma bulk and the sheath regions were investigated. The plasma bulk investigation. In the plasma bulk, the electric field and current density component toward the wall were obtained and employed as boundary conditions for the wall sheath region. In the sheath, a nonstationary model for MP charging in the near wall region was devised. The results are discussed.

The free boundary plasma jet expansion model was extended to a quasineutral plasma jet containing multiply charged ions expanding in an axial magnetic field. Results showed that the different charged ion species can be spatially separated because of the existence of an electric field in the quasineutral plasma. The mean charge state distribution is strongly nonuniform. Calculated and experimental radial distributions of different charged species were in good qualitative agreement.

The expansion of low-density plasma jets in an axial magnetic field in a disk-shaped anode vacuum arc was investigating using a two-dimensional model. Sourceless steady-state hydrodynamic equations were utilized to model the plasma expansion while the anode was modeled as a current and plasma carrier. Results showed that the self-magnetic field had no effect on plasma jet shape, velocity, density or on the current density flow for arc currents.

The reflection of macroparticles, generated by a vacuum arc, from a substrate biased negatively with respect to the surrounding plasma is considered. Charging of macroparticle in the near-substrate sheath and its influence on the macroparticle motion were taken into account. It was found that macroparticles can be either reflected or attracted to the substrate depending strongly on the ion current density. The possibility of macroparticle reflection increases with negative bias voltage and saturates at about a few hundred volts. Index Terms - Macroparticle, sheath, vacuum arc plasma.

Small, lightweight low-power micro-cathode arc thrusters (µCATs) with micronewton thrust are well suited to the altitude control of small satellites like CubeSats. For some applications (orbit raising, maneuvering) their thrust level needs to be improved. A possible approach for this could be the two-staged thruster—a micro-cathode thruster with a magnetoplasmadynamic (MPD) stage and an external magnetic field. In this article, we discuss some discharge features that such a two-stage µCAT-MPD experiences in each configuration of the magnetic field—formed with either a permanent magnet, or a pulsed magnetic coil. We found that in both configurations of the magnetic field, the thrust can be enhanced significantly (up to factor of 10) after some threshold voltage is applied to the second stage. The pulsed magnetic coil ensures better controllability of the magnetic field; however, it causes an undesirable time delay between the plasma generation moments in both stages, which consequently results in a moderate thrust increase. The permanent magnet provides a stable thrust increase; however, it cannot be switched off, which seems to be impractical for its use in micro-satellites. In both magnetic field configurations, the emissive electromagnetic noise level was found to be low-frequency (within tens of kHz) and quite moderate in amplitude, and mechanical noise was found to be two orders of magnitude lower than the thrust generated in the normal working regime. [ABSTRACT FROM AUTHOR]

Global model of atmospheric-pressure anodic arc in helium is developed. This type of discharge is currently used for efficient synthesis of various carbon nanostructures including carbon nanotubes. The model features include coupling between interelectrode plasma and electrodes, current continuity at electrodes, thermal regime of electrodes, and anode erosion. It is taken into account that arc radius increases linearly with the arc current according to experimental observation. Results indicate that substantial fraction of the current at the cathode is conducted by ions (0.7–0.9 of the total current). Calculated anode erosion rate and nonmonotonic voltage-current characteristic of the arc predicted by the model are in agreement with experimental data. It is concluded that nonmonotonic behavior of the arc voltage can be only reproduced by considering experimentally observed dependence of the arc radius on arc current. [ABSTRACT FROM AUTHOR]