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We present a topical drug delivery mechanism through the ear canal to the middle and inner ear using liposomal nanoparticles without disrupting the integrity of the tympanic membrane. The current delivery method provides a noninvasive and safer alternative to transtympanic membrane injections, ear tubes followed by ear drops administration, and systemic drug formulations. We investigate the capability of liposomal NPs, particularly transfersomes (TLipo), used as drug delivery vesicles to penetrate the tympanic membrane (TM) and round window membrane (RWM) with high affinity, specificity, and retention time. The TLipo is applied to the ear canal and found to pass through the tympanic membrane quickly in 3 h post drug administration. They are identified in the middle ear cavity 6 h and in the inner ear 24 h after drug administration. We performed cytotoxicity in vitro and ototoxicity in vivo studies. Cell viability shows no significant difference between the applied TLipo concentration and control. Furthermore, auditory brainstem response (ABR) reveals no hearing loss in 1 week and 1 month post-administration. Immunohistochemistry results demonstrate no evidence of hair cell loss in the cochlea at 1 month following TLipo administration. Together, the data suggested that TLipo can be used as a vehicle for topical drug delivery to the middle ear and inner ear.

The use of intraperitoneal administration of nanoparticles has been reported to facilitate higher concentrations of nanoparticles in metastatic peritoneal tumors. While this strategy is appealing for limiting systemic exposure of nanocarrier delivered toxic cargoes and increasing nanoparticle concentrations in avascular peritoneal tumors, little is known about the mechanism of nanoparticle accumulation on tumor tissues and currently, no nanoparticle-based product has been approved for intraperitoneal delivery. Here, we investigated the nanoparticle-specific characteristics that led to increased peritoneal tumor accumulation using MCM-41 type mesoporous silica nanoparticles as our model system. We also investigated the components of the peritoneal tumor stroma that facilitated nanoparticle-tumor interaction. The tumor extracellular matrix is the main factor driving these interactions, specifically the interaction of nanoparticles with collagen. Upon disruption of the collagen matrix, nanoparticle accumulation was reduced by 50%. It is also notable that the incorporation of targeting ligands did not increase overall tumor accumulation in vivo while it significantly increased nanoparticle accumulation in vitro. The use of other particle chemistries did not grossly affect the tumor targetability, but additional concerns arose when those tested particles exhibited significant systemic exposure. Mesoporous silica nanoparticles are advantageous for intraperitoneal administration for the treatment of peritoneal metastasis due to their physical stability, tumor targetability, strong interaction with the collagen matrix, and extended peritoneal residence time. Maximizing nanoparticle interaction with the tumor extracellular matrix is critical for developing strategies to deliver emerging therapeutics for peritoneal cancer treatment using nanocarriers.

Otitis media (OM) or middle ear infection is one of the most common diseases in young children around the world. The diagnosis of OM is currently performed using an otoscope to detect middle ear fluid and inflammatory changes manifested in the tympanic membrane. However, conventional otoscopy cannot visualize across the tympanic membrane or sample middle ear fluid. This can lead to low diagnostic certainty and overdiagnoses of OM. To improve the diagnosis of OM, we have developed a short-wave infrared (SWIR) otoscope in combination with a protease-cleavable biosensor, 6QC-ICG, which can facilitate the detection of inflammatory proteases in the middle ear with an increase in contrast. 6QC-ICG is a fluorescently quenched probe, which is activated in the presence of cysteine cathepsin proteases that are up-regulated in inflammatory immune cells. Using a preclinical model and custom-built SWIR otomicroscope in this proof-of-concept study, we successfully demonstrated the feasibility of robustly distinguishing inflamed ears from controls (p = 0.0006). The inflamed ears showed an overall signal-to-background ratio of 2.0 with a mean fluorescence of 81 ± 17 AU, while the control ear exhibited a mean fluorescence of 41 ± 11 AU. We envision that these fluorescently quenched probes in conjunction with SWIR imaging tools have the potential to be used as an alternate/adjunct tool for objective diagnosis of OM.

Cancer is a major health burden due to the overall high mortality and physical impairment associated with it. Several factors play relevant roles in cancer prognosis, including the progression stage of the disease. Diagnosing tumors at an early stage is challenging due to the absence or nonspecificity of symptoms and overall lack of specificity and sensitivity of diagnostic methods. Several improvements have been made in past decades, especially with emerging molecular diagnostic tools. Nonetheless, imaging tumor tissues via anatomically oriented tools is still challenging, and the development of new platforms to deliver contrasts/reporters to tumors is a promising strategy to improve the current state of tumor imaging. In this chapter, major aspects related to tumor imaging in vivo are discussed, highlighting the advantages and limitations of major imaging techniques such as X-ray computed tomography, magnetic resonance imaging, positron emission tomography, and optical imaging. Novel nanoparticle–based platforms are also explored and discussed with respect to their contribution toward improving tumor imaging sensitivity and specificity when compared with small-molecule contrast agents.

Mesoporous α-MoO3–x combined with poly(diallyldimethylammonium chloride)–functionalized reduced graphene oxide (PDDA–rGO) is introduced as an inexpensive and efficient oxygen reduction reaction (ORR) catalyst. The mesoporous catalysts are wrapped by conductive rGO sheets via an electrostatic interaction induced by a PDDA polyelectrolyte. The thermal interaction of PDDA with MoO3 efficiently reduces the metal oxide to MoO3–x at 400–600 °C, creating a surface oxygen vacancy. Through a combination of density functional theory and experiments, the role of the surface oxygen vacancy sites in the ORR activity of MoO3–x is identified. For the first time, all the energy barriers against ORR are calculated at each step for MoO3 with no oxygen vacancies and MoO3–x with surface oxygen vacancies. It is shown that the presence of an Mo4+‐vO•• oxygen vacancy site on the surface significantly reduces the energy barriers against ORR in the reaction pathways. An overpotential of 0.86 V (vs a reversible hydrogen electrode)...

The presence of oxygen vacancy sites fundamentally affects physical and chemical properties of materials. In this study, a dipole-containing interaction between poly(diallyldimethylammonium chloride) PDDA and α-MoO3 is found to enable high-concentrations of surface oxygen vacancies. Thermal annealing under Ar resulted in negligible reduction of MoO3 to MoO3–x with x = 0.03 at 600 °C. In contrast, we show that the thermochemical reaction with PDDA polyelectrolyte under Ar can significantly reduce MoO3 to MoO3–x with x = 0.36 (MoO2.64) at 600 °C. Thermal annealing under H2 gas enhanced the substoichiometry of MoO3–x from x = 0.62 to 0.98 by using PDDA at the same conditions. Density functional theory calculations, supported by experimental analysis, suggest that the vacancy sites are created through absorption of terminal site oxygen (Ot) upon decomposition of the N–C bond in the pentagonal ring of PDDA during the thermal treatment. Ot atoms are absorbed as ionic O– and neutral O2–, creating Mo5+-vO· and Mo...

Metal oxides have been widely studied in recent years to replace commercial graphite anodes in lithium ion batteries. Among the metal oxides, manganese oxide has a high theoretical capacity, low cost, and is environmentally friendly. However, many MnO materials have shown limited reaction reversibility and poor conversion kinetics. To understand why, in this paper we investigate the mechanism, kinetics, and reversibility for the solid-state conversion reaction of MnO with Li+. We definitively show, for the first time, that during repeated reaction cycles, multiple reaction pathways occur that lead not only to the reformation of MnO but also higher oxidation-state Mn3O4—which when combined with the poor intrinsic electronic conductivity of both manganese oxide species results in a rapid loss in the amount of charge that can be stored in these materials. Learning this, the approach in this study was to use cobalt doping to concomitantly stabilize the redox behavior of manganese (allowing for the gradual tra...

Hollow spherical structures of ternary bismuth molybdenum oxide doped with samarium (Bi2–xSmxMoO6) were successfully synthesized via development of a Pluronic P123 (PEO20-PPO70-PEO20)-assisted solvothermal technique. Density functional theory calculations have been performed to improve our understanding of the effects of Sm doping on the electronic band structure, density of states, and band gap of the material. The calculations for 0 ≤ x ≤ 0.3 revealed a considerably flattened conduction band minimum near the Γ point, suggesting that the material can be considered to possess a quasi-direct band gap. In contrast, for x = 0.5, the conduction band minimum is deflected toward the U point, making it a distinctly indirect band gap material. The effects of a hollow structure as well as Sm substitution on the absorbance and fluorescence properties of the materials produced increased emission intensities at low Sm concentrations (x = 0.1 and 0.3), with x = 0.1 displaying a peak photoluminescence intensity 13.2 ti...

Metal oxide compounds are a promising category of materials for the Li-ion battery anode due to their high theoretical capacity and natural abundance, although acceptable capacity retention and cycle life has not yet been achieved. In this work, we significantly improve the cycle life of manganese oxide through simultaneous cobalt doping and impregnation with a low 10% mass loading of carbon nanotubes (CNTs). The MnO/CNT anode was able to retain its capacity of ca. 550 mAh/g over 300 cycles at 400 mA/g. To the best of our knowledge, this is among the best cycle life data reported for any MnO/CNT based anode. The composite also shows excellent rate capability, still supplying 400 mAh/g at a current rate of 1600 mA/g.

The thermal properties of yttrium-stabilized lithium zirconate phosphate [LZP: Li1+x+yYxZr2−x(PO4)3 with x = 0.15, −0.2 ≤ y ≤ 0.4 and with x = 0.0, y = 0.0] are presented over a wide temperature range from 30 to 973 K, elucidating the interplay between structural phase transformations and thermal properties in a solid state superionic conducting material. At room temperature, the thermal conductivity decreases by more than 75% as the stoichiometry is changed from lithium deficient to excess and increases with increasing temperature, indicative of defect-mediated transport in the spark plasma sintered materials. The phase transformations and their stabilities are examined by x-ray diffraction and differential scanning calorimetry and indicate that the Y3+ substitution of Zr4+ is effective in stabilizing the ionically conductive rhombohedral phase over the entire temperature range measured, the mechanism of which is found through ab initio theoretical calculations. These insights into thermal transport of LZP superionic conductors are valuable as they may be generally applicable for predicting material stability and thermal management in the ceramic electrolyte of future all-solid-state-battery devices.

MnO is an electrically insulating material which limits its usefulness in lithium ion batteries. We demonstrate that the electrochemical performance of MnO can be greatly improved by using oxygen-functional groups created on the outer walls of multiwalled carbon nanotubes (MWCNTs) as nucleation sites for metal oxide nanoparticles. Based on the mass of the active material used in the preparation of electrodes, the composite conversion-reaction anode material Mn1-x Co x O/MWCNT with x = 0.2 exhibited the highest reversible specific capacity, 790 and 553 mAhg-1 at current densities of 40 and 1600 mAg-1, respectively. This is 3.1 times higher than that of MnO/MWCNT at a charge rate of 1600 mAg-1. Phase segregation in the [Formula: see text] nanoparticles was not observed for x ≤ 0.15. Capacity retention in x = 0, 0.2, and 1 electrodes showed that the corresponding specific capacities were stabilized at 478, 709 and 602 mAhg-1 respectively, after 55 cycles at a current density of 400 mAg-1. As both MnO and CoO exhibit similar theoretical capacities and MnO/MWCNT and CoO/MWCNT anodes both exhibit lower performance than Mn0.8Co0.2O/MWCNT, the improved performance of the [Formula: see text] alloy likely arises from beneficial synergistic interactions in the bimetallic system.

This work describes our discovery of the dominant role of highly charged interfaces on the electrothermal transport properties of PbS, along with a method to reduce the barrier potential for charge carriers by an order of magnitude. High temperature thermoelectrics such as PbS are inevitably exposed to elevated temperatures during postsynthesis treatment as well as operation. However, we observed that as the material was heated, large concentrations of sulfur vacancy (VS̈) sites were formed at temperatures as low as 266 °C. This loss of sulfur doped the PbS n-type and increased the carrier concentration, where these excess electrons were trapped and immobilized at interfacial defect sites in polycrystalline PbS with an abundance of grain boundaries. Sulfur deficient PbS0.81 exhibited a large barrier potential for charge carriers of 0.352 eV, whereas annealing the material under a sulfur-rich environment prevented VS̈ formation and lowered the barrier by an order of magnitude to 0.046 eV. Through ab initio calculations, the formation of VS̈ was found to be more favorable on the surface compared to the bulk of the material with a 1.72 times lower formation energy barrier. These observations underline the importance of controlling interface-vacancy effects in the preparation of bulk materials comprised of nanoscale constituents.

Hollow spherical structures of ternary bismuth molybdenum oxide doped with samarium (Bi

Li ion batteries (LIBs) have been the leading technology in the portable electronics market since their discovery by Sony in the 1990s. Commercially, their setup is constituted by a graphite anode, a lithium metal oxide cathode and LiPF6 dissolved in a mixture of carbonates as electrolyte, characterized by a maximum energy specific density 150 Wh/Kg [1]. However, the needs of newer and cleaner forms of energy is pushing lithium ion batteries towards higher scale applications, such as the electric grid or automotive, requiring the energy and power density to be at least doubled in the near future. Materials advances at both sides of the cell have been actively investigated for several years. The cathodic side of the cell presents very few choices of materials that are suitable to be used in LIBs (LiCoO2, LiMnO2, LiFeO4), all with a theoretical capacity lower than 300 mAh/g, and even lower practically achievable capacity. At the anode, there is a much wider choice of active materials. Silicon has been one of the most widely investigated options in recent years because of its very high theoretical capacity (>3000 mAh/g) and availability. However, pure silicon materials show very rapid deep capacity fade due to the large volumetric expansion occurring during the alloying/dealloying electrochemical reaction (more than 250% of the initial volume). To mitigate this, several materials and operational adjustments have been made and modern silicon composites are only able to achieve a capacity ca. 1000 mAh/g, only 1/3 of the theoretical capacity [2]. Moreover, reference [3] showed that, due to the cathodic limitation of the cell, there is a “capacity penalty” when the anode material capacity is too much larger than the cathode material, and the anode capacity should only be around 700 mAh/g (until new cathode materials are discovered) to fully realize improvements to the overall cell performance. This opens up the periodic table to a wide number of available chemistries including metal oxides [4] which have been the focus of many electrochemical studies so far because of their higher capacity relative to graphite and environmental friendliness. Among the metal oxides, manganese oxides are attractive because they are inexpensive and highly available [5]. Unfortunately, to date few studies have been shown with acceptable capacity and retention have been reported, particularly under realistic operating conditions. In this work, our team will discuss the synthesis of a novel bi-metallic Mn/Co oxide active material imbedded into a low loading multiwalled carbon nanotubes matrix, as shown in Figure 1. We will show the impact of cobalt doping on half-cell performance. Different Cobalt dopant contents (0%,5%,10%,15% and 20%) were prepared and their electrochemical performance was tested, including capacity retention (Figure 2) and rate capability up to 1600 mA/g. Lastly, Na was used as a doping as well, increasing the performance of the manganese active material, which can be tied to enhancement in the electronic conductivity. References. M.M. Thackeray, C. Wolverton and E.D. Isaacs, Energy and Environmental Science, 5, (2012), 7854. T. Osaka, H. Nara, T. Momma and T. Yokoshima, J. Mater. Chem. A, 2, (2014) 883. M. Karulkar, J. Power Sources, 273 (2015) 1194-1201. N. Spinner, L. Zhang and W.E. Mustain, J. Mat. Chem. A, 2(6) (2014) 1627. L. Li, A.R.O. Raji and J.M. Tour, Advanced Materials, 25, (2013), 6298. Figure 1