Topical Delivery of Elastic Liposomal Vesicles for Treatment of Middle and Inner Ear Diseases.

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.

Short-Wave Infrared Fluorescence Chemical Sensor for Detection of Otitis Media.

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.

Tumor-mesoporous silica nanoparticle interactions following intraperitoneal delivery for targeting peritoneal metastasis.

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.

Polyelectrolyte-Assisted Oxygen Vacancies: A New Route to Defect Engineering in Molybdenum Oxide.

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 Mo4+-vO·· vacancy bipolarons and polarons, respectively. X-ray photoemission spectroscopy peak analysis indicates the ratio of charged to neutral molybdenum ions in the PDDA-processed samples increased from Mo4+/Mo6+ = 1.0 and Mo5+/Mo6+ = 3.3 when reduced at 400 °C to Mo4+/Mo6+ = 3.7 and Mo5+/Mo6+ = 2.6 when reduced at 600 °C. This is consistent with our ab initio calculation where the Mo4+-vO·· formation energy is 0.22 eV higher than that for Mo5+-vO· in the bulk of the material and 0.02 eV higher on the surface. This study reveals a new paradigm for effective enhancement of surface oxygen vacancy concentrations essential for a variety of technologies including advanced energy conversion applications such as electrochemical energy storage, catalysis, and low-temperature thermochemical water splitting.

Effect of cobalt alloying on the electrochemical performance of manganese oxide nanoparticles nucleated on multiwalled carbon nanotubes.

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.

Block Copolymer-Assisted Solvothermal Synthesis of Hollow Bi2MoO6 Spheres Substituted with Samarium.

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 times higher than for the undoped bulk sample. Subsequent increases in the Sm concentration resulted in quenching of the emission intensity, indicative of the onset of a quasi-direct-to-indirect electronic band transition. These results indicate that both mesoscale structuring and Sm doping will be promising routes for tuning optoelectronic properties for future applications such as catalysis and photocatalysis.