Corrugated surface microparticles with chitosan and levofloxacin for improved aerodynamic performance.

Corrugated surface microparticles comprising levofloxacin (LEV), chitosan and organic acid were prepared using the 3-combo spray drying method. The amount and the boiling point of the organic acid affected the degree of roughness. In this study, we tried to improve the aerodynamic performance and increase aerosolization by corrugated surface microparticle for lung drug delivery efficiency as dry powder inhaler. HMP175 L20 prepared with 175 mmol propionic acid solution was corrugated more than HMF175 L20 prepared with 175 mmol formic acid solution. The ACI and PIV results showed a significant increase in aerodynamic performance of corrugated microparticles. The FPF value of HMP175 L20 was 41.3% ± 3.9% compared with 25.6% ± 7.7% of HMF175 L20. Corrugated microparticles also showed better aerosolization, decreased x-axial velocity, and variable angle. Rapid dissolution of drug formulations was observed in vivo. Low doses administered to the lungs achieved higher LEV concentrations in the lung fluid than high doses administered orally. Surface modification in the polymer-based formulation was achieved by controlling the evaporation rate and improving the inhalation efficiency of DPIs.

Artificial Action Potential and Ionic Power Device Inspired by Ion Channels and Excitable Cell.

In vivo, the membrane potential of the excitable cell working by ion gradients plays a significant role in bioelectricity generation and nervous system operation. Conventional bioinspired power systems generally have adopted ion gradients, but overlook the functions of ion channels and Donnan effect to generate efficient ion flow in the cell. Here, cell-inspired ionic power device implementing the Donnan effect using multi-ions and monovalent ion exchange membranes as artificial ion channels is realized. Different ion-rich electrolytes on either side of the selective membrane generate the ion gradient potentials with high ionic currents and reduce the osmotic imbalance of the membrane. Based on this device, the artificial neuronal signaling is presented by the mechanical switching system of the ion selectivity like mechanosensitive ion channels in a sensory neuron. Compared with reverse electrodialysis, which requires a low concentration, a high-power device with ten times the current and 8.5 times the power density is fabricated. This device activates grown muscle cells by increasing power through serial connection like an electric eel, and shows the possibility of an ion-based artificial nervous system.

Inhalable Nano-Dimpled Microspheres Containing Budesonide-PLGA for Improved Aerodynamic Performance.

Introduction: Dry powder inhalations are an attractive pharmaceutical dosage form. They are environmentally friendly, portable, and physicochemical stable compared to other inhalation forms like pressurized metered-dose inhalers and nebulizers. Sufficient drug deposition of DPIs into the deep lung is required to enhance the therapeutic activity. Nanoscale surface roughness in microparticles could improve aerosolization and aerodynamic performance. This study aimed to prepare microspheres with nanoscale dimples and confirm the effect of roughness on inhalation efficiency. Methods: The dimpled-surface on microspheres (MSs) was achieved by oil in water (O/W) emulsion-solvent evaporation by controlling the stirring rate. The physicochemical properties of MSs were characterized. Also, in vitro aerodynamic performance of MSs was evaluated by particle image velocimetry and computational fluid dynamics. Results: The particle image velocimetry results showed that dimpled-surface MSs had better aerosolization, about 20% decreased X-axial velocity, and a variable angle, which could improve the aerodynamic performance. Furthermore, it was confirmed that the dimpled surface of MSs could cause movement away from the bronchial surface, which helps the MSs travel into the deep lung using computational fluid dynamics. Conclusion: The dimpled-surface MSs showed a higher fine particle fraction value compared to smooth-surface MSs in the Andersen Cascade Impactor, and surface roughness like dimples on microspheres could improve aerosolization and lung deposition.

Strong and Tough Nacre-Inspired Graphene Oxide Composite with Hierarchically Similar Structure.

We report a graphene oxide (GO)-based composite, featuring GO/cross-linking agent (CA) nanoparticles, inspired by a nacre-like hierarchical structure present in nature. The as-prepared GO/CA composite was powdered to nanoscale particles and then mixed with pure GO to be GO/CA/GO (GCG) composite forming hierarchical GO/CA nanoasperities on the GO surface. The strength and toughness of the nacre-inspired GCG composite films were simultaneously improved by adjusting the nanoparticle concentration and hierarchical level of the GO-based films. Compared to pristine GO films and GO/CA composites, which exhibit a low level of hierarchy in their structures, the tensile strength and toughness of the GCG composites with higher hierarchy were enhanced 3.1 and 1.6 times and 47.6 and 10.9 times, respectively. Furthermore, a plausible mechanism of increasing mechanical properties based on nanoscale asperities and homogeneous interactions between GO and CA has been discussed.

Asymmetric Dichroic Colors in Stretchable Film with Embedded Au/Ag Alloy Nanoparticles.

We present a new type of stretchable dichroic film in which Au and Ag alloy nanoparticles (NPs) are dispersed in polydimethylsiloxane (PDMS). The alloy NPs are synthesized with different atomic compositions and sizes to modulate their plasmonic resonance frequencies and absorption and scattering cross sections. The PDMS dichroic film in which 100 nm alloy NPs with a Au/Ag ratio of 7:3 are dispersed shows exotic optical properties under tensile strain. When 40% tensile strain is applied, the film exhibits a strain-sensitive transmission and strain-insensitive reflection behavior in which the transmittance is increased up to 2.6 times, whereas the reflectance remains unchanged. Moreover, we demonstrate a stretchable anticounterfeiting film and a flexible dichroic sculpture fabricated with the PDMS composite. This work demonstrates a new type of plasmonic application that has great potential in various applications, such as special-purpose optical films, security patterns, and smart windows.

A Wearable All-Gel Multimodal Cutaneous Sensor Enabling Simultaneous Single-Site Monitoring of Cardiac-Related Biophysical Signals.

The human cutaneous sensory organ is a highly evolved biosensor that is efficient, sensitive, selective, and adaptable. Recently, with the development of various materials and structures inspired by sensory organs, artificial cutaneous sensors have been widely studied. In this study, the acquisition of biophysical signals is demonstrated at one point on the body using a wearable all-gel-integrated multimodal sensor composed of four element sensors, inspired by the slow/rapid adapting functions of the skin sensory receptors. The gel-type sensors ensure flexibility, compactness, portability, adherence, and integrity. The wearable all-gel multimodal sensor is easily attached to the wrist and simultaneously gathers blood pressure (BP), electrocardiogram (ECG), electromyogram (EMG), and mechanomyogram (MMG) signals related to cardiac and muscle health. Human activity causes muscle contraction, which affects blood flow; therefore, the relationship between the muscle and heart is crucial for screening and predicting heart health. Cardiac health is monitored by obtaining the two types of phase time differences (i.e., Δtbe : BP and ECG, Δtem : ECG and MMG) generated during muscle movement. The suggested multimodal sensor has potential applicability in monitoring biophysical conditions and diagnosing cardiac-related health problems.

Wearable Triboelectric Strain-Insensitive Pressure Sensors Based on Hierarchical Superposition Patterns.

Recently, wearable triboelectric sensors capable of self-powering, which can be widely used in artificial skin and robotics, have received much attention. Herein, we develop a stretchable triboelectric pressure sensor with a new pattern by superimposing two patterns using both polystyrene beads and UV-ozone treatment. This patterned structure works more sensitively to pressure than a general planar and one-kind patterned structure. The sensor is constructed by sandwiching styrene butadiene rubber (SBR) and poly(dimethylsiloxane) (PDMS). It demonstrates a high sensitivity of 0.078 kPa-1 (0-20 kPa), a low detection limit (1.2 kPa), and pressure sensitivity maintained under 40% strain. The detection behavior of the strain-insensitive triboelectric sensor against pressure is very consistent with the simulation based on the theory. In applications, we successfully detect various human motions, not only small motions such as bending fingers but also large motions such as standing up and raising arms.

Self-Powered, Stretchable, and Wearable Ion Gel Mechanoreceptor Sensors.

Mechanoreceptors in human skin are important and efficient cutaneous sensors that are highly sensitive, selective, and adaptive to the environment. Among these, Merkel disk (MD) and cilia are capable of sensing an external mechanical force through a receptor with a sharp pillar-like structure at its end. Then, the signal of the action potential is generated by pumping Na+ ions through ion channels. In this study, a self-powered, stretchable, and wearable gel mechanoreceptor sensor is developed inspired by the structural features of the MD and cilia with sharp tips and the signaling characteristics of mechanoreceptor ion migration. Poly(vinylidene fluoride-co-trifluoroethylene) gel is used to implement a self-powered system, and polyvinylchloride-based elastic gel is utilized to detect sensing signals based on charge transfer and distribution. The surface of all gels is that of a conical structure to achieve high sensor sensitivity and conformal contact with a target surface. In addition, using the developed sensors, various biological signals related to pressure/strain occurring in the human body (e.g., blood pressure (BP), muscle movement, and motion) are acquired. Furthermore, the behavior of arterial BP was investigated during the contraction and relaxation of the muscles.

Physicochemical characterization of dapagliflozin and its solid-state behavior in stress stability test.

As an active pharmaceutical ingredient, dapagliflozin propanediol monohydrate (D-PD) has been used in the solvated form consisting of dapagliflozin compounded with (S)-propylene glycol and monohydrate at a 1:1:1 ratio. However, dapagliflozin propanediol loses the solvent's reduced lattice structure at slightly higher temperatures. Due to its sensitive solid-state stability, the temperature and humidity are strictly controlled during the production and storage of dapagliflozin. Thus, crystalline molecular complexes containing pharmaceutical salts, solvates, monohydrates, and cocrystals have recently been developed as alternative strategies. This study investigated the dapagliflozin free base (D-FB), D-PD, and dapagliflozin l-proline cocrystals (D-LP). Their solid-state behavior was also evaluated in stress stability studies. The compounds were analyzed using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, dynamic vapor sorption (DVS), and powder rheology testing. In addition, Carr's index, the Hausner ratio, contact angle, and intrinsic dissolution rate were calculated. Dapagliflozin exhibited distinct physical properties depending upon the differences in solid form and also showed significant differences in solid-state behavior in the stress stability test. In conclusion, D-LP was superior to D-FB or D-PD in physicochemical and mechanical properties.

Economical Auto Moment Limiter for Preventing Mobile Cargo Crane Overload.

This study presents a computational method called economical auto moment limiter (eAML) that prevents a mobile cargo crane from being overloaded. The eAML detects and controls, in real time, crane overload without using boom stroke sensors and load cells, which are expensive items inevitable to existing AML systems, hence, being competitive in price. It replaces these stroke sensors and load cells that are used for the crane overload measurement with a set of mathematical formula and control logics that calculates the lifting load being handled under crane operation and the maximum lifting load. By calculating iterative them using only a pressure sensor attached under the derrick cylinder and the boom angle sensor, the mathematical model identifies the maximum descendible angle of the boom. The control logic presents the control method for preventing the crane overload by using the descendible angle obtained by the mathematical model. Both the mathematical model and the control logic are validated by rigorous simulation experiments using MATLAB on two case instances each of which eAML is used and not used, while changing the pressures on the derrick cylinder and the boom angle. The effectiveness and validity of the method are confirmed by comparing the outputs obtained by the controlled experiments performed by using a 7.6 ton crane on top of SCS887 and a straight-type maritime heavy-duty crane along with eAML. The effects attributed to the load and the wind speed are quantified to verify the reliability of eAML under the changes in external variables.

The Effect of Particle Size and Surface Roughness of Spray-Dried Bosentan Microparticles on Aerodynamic Performance for Dry Powder Inhalation.

The purpose of this study was to prepare spray dried bosentan microparticles for dry powder inhaler and to characterize its physicochemical and aerodynamic properties. The microparticles were prepared from ethanol/water solutions containing bosentan using spray dryer. Three types of formulations (SD60, SD80, and SD100) depending on the various ethanol concentrations (60%, 80%, and 100%, respectively) were used. Bosentan microparticle formulations were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, differential scanning calorimetry, Fourier-transform infrared spectroscopy, dissolution test, and in vitro aerodynamic performance using Andersen cascade impactor™ (ACI) system. In addition, particle image velocimetry (PIV) system was used for directly confirming the actual movement of the aerosolized particles. Bosentan microparticles resulted in formulations with various shapes, surface morphology, and particle size distributions. SD100 was a smooth surface with spherical morphology, SD80 was a rough surfaced with spherical morphology and SD60 was a rough surfaced with corrugated morphology. SD100, SD80, and SD60 showed significantly high drug release up to 1 h compared with raw bosentan. The aerodynamic size of SD80 and SD60 was 1.27 µm and SD100 was 6.95 µm. The microparticles with smaller particle size and a rough surface aerosolized better (%FPF: 63.07 ± 2.39 and 68.27 ± 8.99 for SD60 and SD80, respectively) than larger particle size and smooth surface microparticle (%FPF: 22.64 ± 11.50 for SD100).

Angle-Insensitive Transmission and Reflection of Nanopatterned Dielectric Multilayer Films for Colorful Solar Cells.

Aesthetically appealing photovoltaic (PV) panels with colorful layers are used in numerous applications involving color matching with the surroundings. To develop a colored film for a PV system, appropriate optical properties such as high transparency and low angle sensitivity are necessary because the colored layers can reduce the efficiency of the PV system by causing variations in the transmittance and angle of incidence. Herein, we propose a facile fabrication method for bioinspired three-dimensional (3D) photonic crystal (PC) films that exhibit broad angle-insensitive transmission and reflection, for application in colorful PV. This structure, patterned on a sequentially stacked 11-layer film of SiO2 and TiO2, is fabricated via nanoimprint lithography and a one-step dry-etching process, without using a metal mask. The changes in transmission and reflection are observed via ultraviolet-visible spectroscopy and from the reflected images obtained under various angles. The transmittance dips of the 3D PC film shift by less than 10 nm in wavelength, for angles from 0 to 45°, indicating low angle dependency. In addition, the change in the observed color, with respect to the viewing position, is less in the fabricated film. Once the 3D PC film was added to a commercial PV cell, it exhibited a higher efficiency (approximately 6% upper) when compared to a cell with a one-dimensional PC film, during the duration of the experiment, from 0 to 30°. Thus, the proposed method demonstrates excellent potential for developing structural color films for achieving aesthetically appealing PV cells.

Nonlinearly Frequency-Adaptive, Self-Powered, Proton-Driven Somatosensor Inspired by a Human Mechanoreceptor.

In the human skin, it has been well known that several mechanoreceptors uniquely sense external stimuli with specific frequencies and magnitudes. With regard to sensitivity, the output response shows nonlinearity depending on the frequency magnitude of the stimulus. We demonstrate a self-powered proton-driven solid-state somatosensor, which mimics a unique nonlinear response and intensity behavior of human mechanoreceptors. For this, a solid-state sensor is fabricated by combining a piezoelectric film and a proton generation device. The proton injection electrode and the Nafion layer conjugated with sulfonated graphene oxide are used for proton generation and transport. Two types of nonlinear signals from the sensor are similar to the Merkel/Ruffini (low deviation of threshold intensity), and in contrast, the behavior of Pacinian/Meissner (high deviation of threshold intensity) is simultaneously shown. The region of the most responsive frequency is also discriminated according to proton conduction. Moreover, it is asserted that unique signal patterns are obtained from the stimuli of various frequencies, such as respiration, radial artery pulse, and neck vibration, which naturally occur in the human body.

Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution.

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.

Iridescent and Glossy Effect on Polymer Surface Using Micro-/Nanohierarchical Structure: Artificial Queen of the Night Tulip Petals.

Many petals in nature have a hierarchical structure that imparts various optical properties. Among these, the petals of the Queen of the Night tulip exhibit an iridescent and glossy color due to the diffraction and scattering of light. Herein, we report a bioinspired micro-/nanohierarchical structure that mimics Queen of the Night tulip petal surfaces. Using a method that combined soft lithography and UV-ozone treatment, we fabricated nanoscale line patterns with a linewidth of 600 nm on microwrinkles of 15 µm width and 3 µm height. Using optical microscopy in the dark-field mode and monochromatic light diffraction measurements, we found that these hierarchical structures on a poly(dimethylsiloxane) (PDMS) substrate synergistically improved the scattering and diffraction effects, unlike the pristine, nano-, and microstructures. In addition, using a dye-colored PDMS material, we fabricated artificial Queen of the Night petals with iridescent and glossy effects. They show great potential for a range of applications, such as coloring, smart displays, dynamic gratings, and light-control devices.

Preparation, Characterization, and Stability Evaluation of Taste-Masking Lacosamide Microparticles.

Lacosamide (LCM) is a third-generation antiepileptic drug. Selective action of the drug on voltage-gated sodium channels reduces side effects. Oral administration of LCM shows good pharmacokinetic profile. However, the bitter taste of LCM is a barrier to the development of oral formulations. In this study, we aimed to prepare encapsulated LCM microparticles (MPs) for masking its bitter taste. Encapsulated LCM MPs were prepared with Eudragit® E100 (E100), a pH-dependent polymer, by spray drying. Three formulations comprising different ratios of LCM and E100 (3:1, 1:1, and 1:3) were prepared. Physicochemical tests showed that LCM was in an amorphous state in the prepared formulations, and they were not miscible. LCM-E100 (1:3) had a rough surface due to surface enrichment of LCM. Increased E100 ratio in LCM-E100 MPs resulted in better taste-making effectiveness: LCM-E100 (1:1) and LCM-E100 (1:3) showed good taste-masking effectiveness, while LCM-E100 (3:1) could not mask the bitter taste of LCM. Dissolution results of the prepared formulations showed good correlation with taste-masking effectiveness. Nevertheless, high E100 ratio reduced the stability of the prepared formulations. Especially the difference in initial dissolution profile observed for LCM-E100 (1:3) indicated rapid reduction in taste-masking effectiveness and surface recrystallization. Therefore, LCM-E100 formulation in the ratio of 1:1 was selected as the best formulation with good taste-masking effectiveness and stability.

Nacre-Mimetic Graphene Oxide/Cross-Linking Agent Composite Films with Superior Mechanical Properties.

We report a graphene oxide/cross-linking agent (GO/CA) composite inspired by the nacre structure. Based on the "brick-and-mortar" concept of nacre, graphene oxide and a cross-linking agent are covalently conjugated in the form of nacre. The mechanical characteristics of the nacre-mimetic GO/CA composite film can be controlled by adjusting the preparation method, degree of cross-linking, and cross-linking times. As a result, the cross-linking strategy can drastically enhance the tensile strength [142.9 ± 6.4 MPa (∼2.3-fold)], modulus [4.7 ± 0.36 GPa (∼15.7-fold)], and hardness [917.4 ± 85.7 MPa (∼9.0-fold)], which are superior to those of pristine materials. The cross-linking agent-based chemical bonding method for mechanically improved integration is mainly attributed to the formation of strong cross-linked networks between the GO-based 2D interfaces and CA. The facile fabrication process provides many opportunities to design advanced, robust, and integrated nacre-like GO/CA composites, which can be applied to future aerospace utilizations, electronic protectors, robotic elements, and permeable membranes.

Spectral Sensor Inspired by Cone Photoreceptors and Ion Channels without External Power.

In this study, we focused the mimicking of the cone photoreceptor along with ion channel system, which is similar to real optical system. By realizing the ion channel and photoreceptor based on photoresponsive material and photoelectric film, we achieved the wavelength-selective sensor with self-power ability. For the first time, we combined the photoreceptor and ion channel system without external power. For this, we used the channel membrane with pores coated with light-responsive material. We measured the sensing signals without any external power, because photoelectric film assists the sensitive operation of the ion channel system. As a result, we demonstrated a spectral ion channel sensor triggered by the photoelectric effect. Mimicking the slow and fast responses typically found in cone photoreceptor, when induced light causes photovoltaic effect from the pyrrole-coated polyvinylidene fluoride film, this helps to normally operate the ion channel system with slow and fast responses to the light wavelengths. Consequently, this research opens the new scientific fields to realize the photosensor very similar to the real vision sensory organ.

A low-noise silicon nitride nanopore device on a polymer substrate.

We report a novel low-noise nanopore device employing a polymer substrate. The Si substrate of a fabricated Si-substrate-based silicon nitride (Si3N4) membrane was replaced with a polymer substrate. As such, laser machining was used to make a micro-size hole through the polyimide (PI) substrate, and a thin Si3N4 membrane was then transferred onto the PI substrate. Finally, a nanopore was formed in the membrane using a transmission electron microscope for detection of biomolecules. Compared to the Si-substrate-based device, the dielectric noise was greatly reduced and the root-mean-square noise level was decreased from 146.7 to 5.4 pA. Using this device, the translocation of double-strand deoxyribonucleic acid (DNA) was detected with a high signal/noise (S/N) ratio. This type of device is anticipated to be available for future versatile sequencing technologies.

Preparation and in vitro/in vivo evaluation of PLGA microspheres containing norquetiapine for long-acting injection.

BACKGROUND: Norquetiapine (N-desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required. PURPOSE: The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties. METHODS: NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion-solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition. RESULTS: The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles' long acting properties were maintained. Therefore, good in vitro-in vivo correlation was established. CONCLUSION: In this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.