Chemical Enhancement Research Articles

In vivo skin optical clearing efficacy quantification of clinically compatible agents using line-field confocal optical coherence tomography.

The clinical use of optical methods for in vivo skin imaging is limited by skin strong scattering properties, which reduce image contrast and probing depth. The efficiency of optical methods can be improved by optical clearing (OC). However, for the use of OC agents (OCAs) in a clinical setting, compliance with acceptable non-toxic concentrations is required. OC of in vivo human skin, combined with physical and chemical methods to enhance skin permeability to OCAs, was performed to determine the clearing-effectiveness of biocompatible OCAs using line-field confocal optical coherence tomography (LC-OCT) imaging. Nine types of OCAs mixtures were used in association with dermabrasion and sonophoresis for OC protocol on three volunteers hand skin. From 3D images obtained every 5min for 40min, the intensity and contrast parameters were extracted to assess their changes during the clearing process and evaluate each OCAs mixture's clearing efficacy. The LC-OCT images average intensity and contrast increased over the entire skin depth with all OCAs. The best image contrast and intensity improvement was observed using the polyethylene glycol, oleic acid, and propylene glycol mixture. Complex OCAs featuring reduced component concentrations that meet drug regulation-established biocompatibility requirements were developed and proved to induce significant skin tissues clearing. By allowing deeper observations and higher contrast, such OCAs in combination with physical and chemical permeation enhancers may improve LC-OCT diagnostic efficacy.

Multicomponent SERS imprinted bio-membrane based on eggshell membrane for selective detection of spiramycin in water

A novel imprinting membrane (Ag/CuO/CNTs/Eggshell membrane -Molecularly Imprinted polymeric Membrances, ACCE-MIMs) based on surface enhanced Raman scattering (SERS) is successfully synthesized for the specific detection of spiramycin (SP). Firstly, CNTs and CuO are successively loaded on eggshell membrane (ESM) to increase the uniformity and sensitivity by virtue of the unique reticular structure of CNTs and excellent chemical enhancement of CuO. Through the abundant amino and carboxyl groups on ESM, Ag nanoparticles (Ag NPs) are anchored and growth on the surface of membrane by two in-situ reduction process and form a three-dimensional (3D) architecture. Eventually, the ACCE-MIMs are synthetized by silicon-based sol-gel method. With the help of imprinted polymers, the ACCE-MIMs present anti-interference performance during selective detection. The sensor presents a great liner relationship (R2 = 0.9965) between SP concentration and the Raman peak intensity when the concentration of SP ranges between 1 × 10−6 M ∼1 × 10−12 M. The limit of detection concentration is 1 × 10−12 M and the enhancement factor (EF) is 0.2956 × 107. The ACCE-MIMs exhibits sensitive detection property and this procedure provides a promising future for detection process.

Multi-dimensional plasmonic coupling system for efficient enrichment and ultrasensitive label-free SERS detection of bilirubin based on graphene oxide-Au nanostars and Au@Ag nanoparticles

Rapid and sensitive detection of free bilirubin (BR) is essential for early diagnosis of jaundice and other hepatobiliary diseases. Inspired by sandwich immunoassay strategy, a multi-dimensional plasmonic coupling SERS platform composed of graphene oxide-Au nanostars nanocomposites (GANS NCs) and Au@Ag nanoparticles (NPs) was designed for label-free detection of BR. Specifically, GANS NCs were first prepared, and their excellent SERS activity was ascribed to synergistic enhancement effect of electromagnetic enhancement and chemical enhancement. Furthermore, SERS spectroscopy was used to monitor the adsorption process of BR. Subsequently, secondary reinforcing Au@Ag NPs were directly added, ultimately resulting in a multi-dimensional plasmonic coupling effect. The SERS enhancing mechanism of coupled system was discussed through electromagnetic field simulations. Interestingly, the high-density hotspots generated by strong plasmonic coupling in GANS-Au@Ag substrate could lead to more extraordinary SERS enhancing behavior compared to GANS NCs. Sensing efficiency of the SERS platform was examined by BR with a detection limit down to 10−11 M. Besides, GANS-Au@Ag NCs performed high uniformity and reproducibility. This work not only opens up a new avenue for construction of multi-dimensional plasmonic coupling system, but also offers a new biosensing technology for label-free diagnosis of BR-related diseases, thereby expecting to be applied in clinical diagnosis.

An anisotropic nanobox based core-shell-satellite nanoassembly of multiple SERS enhancement with heterogeneous interface for stroke marker determination

Herein, A novel gold-silver alloy nanobox (AuAgNB)@SiO2-gold nanosphere (AuNP) nanoassembly based on core–shell-satellite structure is fabricated and applied to the surface-enhanced Raman scattering (SERS) detection of S100 calcium-binding protein B protein (S100B). It contains an anisotropic hollow porous AuAgNB core with rough surface, an ultrathin silica interlayer labeled with reporter molecules, and AuNP satellites. The nanoassemblies were systematically optimized by tuning the reporter molecules concentration, silica layer thickness, AuAgNB size, and the size and number of AuNP satellite size. Remarkably, AuNP satellites are adjacent to AuAgNB@SiO2, developing AuAg-SiO2-Au heterogeneous interface. With the strong plasmon coupling between AuAgNB and AuNP satellites, chemical enhancement from heterogeneous interface, and the tip “hot spots” of AuAgNB, the SERS activity of the nanoassemblies was multiply enhanced. Additionally, the stability of nanostructure and Raman signal was significantly improved by the silica interlayer and AuNP satellites. Eventually, the nanoassemblies were applied for S100B detection. It demonstrated satisfactory sensitivity and reproducibility with a wide detection range of 10 fg/mL-10 ng/mL and a limit of detection (LOD) of 1.7 fg/mL. This work based on the AuAgNB@SiO2-AuNP nanoassemblies with multiple SERS enhancements and favorable stability demonstrates the promising application in stroke diagnosis.

Transnasal targeted delivery of therapeutics in central nervous system diseases: a narrative review.

Currently, neurointervention, surgery, medication, and central nervous system (CNS) stimulation are the main treatments used in CNS diseases. These approaches are used to overcome the blood brain barrier (BBB), but they have limitations that necessitate the development of targeted delivery methods. Thus, recent research has focused on spatiotemporally direct and indirect targeted delivery methods because they decrease the effect on nontarget cells, thus minimizing side effects and increasing the patient's quality of life. Methods that enable therapeutics to be directly passed through the BBB to facilitate delivery to target cells include the use of nanomedicine (nanoparticles and extracellular vesicles), and magnetic field-mediated delivery. Nanoparticles are divided into organic, inorganic types depending on their outer shell composition. Extracellular vesicles consist of apoptotic bodies, microvesicles, and exosomes. Magnetic field-mediated delivery methods include magnetic field-mediated passive/actively-assisted navigation, magnetotactic bacteria, magnetic resonance navigation, and magnetic nanobots-in developmental chronological order of when they were developed. Indirect methods increase the BBB permeability, allowing therapeutics to reach the CNS, and include chemical delivery and mechanical delivery (focused ultrasound and LASER therapy). Chemical methods (chemical permeation enhancers) include mannitol, a prevalent BBB permeabilizer, and other chemicals-bradykinin and 1-O-pentylglycerol-to resolve the limitations of mannitol. Focused ultrasound is in either high intensity or low intensity. LASER therapies includes three types: laser interstitial therapy, photodynamic therapy, and photobiomodulation therapy. The combination of direct and indirect methods is not as common as their individual use but represents an area for further research in the field. This review aims to analyze the advantages and disadvantages of these methods, describe the combined use of direct and indirect deliveries, and provide the future prospects of each targeted delivery method. We conclude that the most promising method is the nose-to-CNS delivery of hybrid nanomedicine, multiple combination of organic, inorganic nanoparticles and exosomes, via magnetic resonance navigation following preconditioning treatment with photobiomodulation therapy or focused ultrasound in low intensity as a strategy for differentiating this review from others on targeted CNS delivery; however, additional studies are needed to demonstrate the application of this approach in more complex in vivo pathways.

SERS performance of silver nanoparticle/reduced graphene oxide-coated filter membranes

Polyvinylidene fluoride (PVDF), polyamide (Nylon) and anodic aluminum oxide (AAO) filter membranes were coated with in-situ synthesized silver nanoparticle/reduced graphene oxide (AgNP/rGO) nanocomposite by vacuum filtration, and surface-enhanced Raman scattering (SERS) performance of the prepared substrates was investigated using Rhodamine 6G (R6G) as a probe molecule. Analyte solutions were applied by drop casting and penetrated into the flexible PVDF and Nylon-based substrates within minutes, enabling very fast SERS measurements; however, this step took up to 2 hrs in the rigid AAO-based substrate. Scanning electron microscopy and Energy-dispersive X-ray spectroscopy mapping results showed that filter membrane surfaces were completely covered with AgNP/rGO nanocomposite at which AgNPs were uniformly distributed on rGO flakes; however, some large, partially reduced or unreduced GO flakes decorated with AgNP agglomerates (AgNP/GO) were also observed. Higher SERS signals were generally obtained from these AgNP/GO flakes compared to the AgNP/rGO coated regions, since they contain higher amount of oxygen-rich functional groups which enabled a higher chemical and electromagnetic enhancement in SERS signals. All the substrates could detect 10−7 M R6G even after being stored in a vacuum desiccator for 3 months, indicating that AgNP/rGO coated filter membranes are promising as stable SERS substrates thanks to their long shelf life.

Highly sensitive technique for detection of adulterants in centella herbal samples using surface enhanced Raman spectroscopy (SERS)

The trace level detection of adulterants in food, nutritional supplements and medicinal herbs is highly challenging in the field of food processing and herbal industries. In addition, laborious sample processing procedures and well trained personnel are required to analyse the samples using conventional analytical equipments. In this study, a highly sensitive technique with minimal sampling processes and human intervention is proposed for the trace amount detection of pesticidal residues in centella powder. Herein, graphene oxide gold (GO-Au) nanocomposite coated parafilm is developed as substrate by simple dropcasting technique to facilitate dual surface enhanced Raman signal. The dual SERS enhancement involving chemical enhancement from graphene and electromagnetic signal enhancement from gold nanoparticles is utilized for detection of chlorpyrifos in the ppm level concentration. The flexible polymeric surfaces could be the better choice for SERS substrates due to their inherent properties such as flexibility, transparency, roughness and hydrophobicity. Among the various types of flexible substrates explored, GO-Au nanocomposites coated parafilm substrates showed better Raman signal enhancement. Parafilm coated with GO-Au nanocomposites is successful in achieving detection limits down to 0.1 ppm of chlorpyrifos in centella herbal powder sample. Thus, the fabricated parafilm based GO-Au SERS substrates could be used as a screening tool at quality control of herbal product manufacturing sectors for trace level detection of adulterants in herbal samples from their unique chemical and structural information.

The Convenience of Polydopamine in Designing SERS Biosensors with a Sustainable Prospect for Medical Application.

Polydopamine (PDA) is a multifunctional biomimetic material that is friendly to biological organisms and the environment, and surface-enhanced Raman scattering (SERS) sensors have the potential to be reused. Inspired by these two factors, this review summarizes examples of PDA-modified materials at the micron or nanoscale to provide suggestions for designing intelligent and sustainable SERS biosensors that can quickly and accurately monitor disease progression. Undoubtedly, PDA is a kind of double-sided adhesive, introducing various desired metals, Raman signal molecules, recognition components, and diverse sensing platforms to enhance the sensitivity, specificity, repeatability, and practicality of SERS sensors. Particularly, core-shell and chain-like structures could be constructed by PDA facilely, and then combined with microfluidic chips, microarrays, and lateral flow assays to provide excellent references. In addition, PDA membranes with special patterns, and hydrophobic and strong mechanical properties can be used as independent platforms to carry SERS substances. As an organic semiconductor material capable of facilitating charge transfer, PDA may possess the potential for chemical enhancement in SERS. In-depth research on the properties of PDA will be helpful for the development of multi-mode sensing and the integration of diagnosis and treatment.

Interpreting chemical enhancements of surface-enhanced Raman scattering

Surface-enhanced Raman scattering (SERS) provides orders of magnitude of enhancements to weak Raman scattering. The improved sensitivity and chemical information conveyed in the spectral signatures make SERS a valuable analysis technique. Most of SERS enhancements come from the electromagnetic enhancement mechanism, and changes in spectral signatures are usually attributed to the chemical enhancement mechanism. As the electromagnetic mechanism has been well studied, we will give an overview of models related to the chemical mechanism, which explain the Raman response in terms of electronic transitions or induced electron densities. In the first class of models based on electronic transitions, chemical enhancements are attributed to changes in transitions of the molecule and new charge transfer transitions. The second class of models relate chemical enhancements to charge flows near the molecule–metal interface by partitioning the induced electron density of the SERS system in real space. Selected examples will be given to illustrate the two classes of models, and connections between the models are demonstrated for prototypical SERS systems.

Polychromatic neutron phase-contrast imaging of weakly absorbing samples enabled by phase retrieval.

The use of a phase-retrieval technique for propagation-based phase-contrast neutron imaging with a polychromatic beam is demonstrated. This enables imaging of samples with low absorption contrast and/or improving the signal-to-noise ratio to facilitate e.g. time-resolved measurements. A metal sample, designed to be close to a phase pure object, and a bone sample with canals partially filled with D2O were used for demonstrating the technique. These samples were imaged with a polychromatic neutron beam followed by phase retrieval. For both samples the signal-to-noise ratios were significantly improved and, in the case of the bone sample, the phase retrieval allowed for separation of bone and D2O, which is important for example for in situ flow experiments. The use of deuteration contrast avoids the use of chemical contrast enhancement and makes neutron imaging an interesting complementary method to X-ray imaging of bone.

Emulsion-Based Gel Loaded with Ibuprofen and Its Derivatives.

The aim of this study was to evaluate the effect of vehicle and chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen (IBU). As a result, semi-solid formulations in the form of an emulsion-based gel loaded with ibuprofen and its derivatives, such as sodium ibuprofenate (IBUNa) and L-phenylalanine ethyl ester ibuprofenate ([PheOEt][IBU]), were developed. The properties of the obtained formulations were examined, including density, refractive index, viscosity, and particle size distribution. The parameters of release and permeability through the pig skin of the active substances contained in the obtained semi-solid formulations were determined. The results indicate that an emulsion-based gel enhanced the skin penetration of IBU and its derivatives compared to two commercial preparations in the form of a gel and a cream. The average cumulative mass of IBU after a 24 h permeation test from an emulsion-based gel formulation through human skin was 1.6-4.0 times higher than for the commercial products. Ibuprofen derivatives were evaluated as chemical penetration enhancers. After 24 h of penetration, the cumulative mass was 1086.6 ± 245.8 for IBUNa and 948.6 ± 87.5 µg IBU/cm2 for [PheOEt][IBU], respectively. This study demonstrates the perspective of the transdermal emulsion-based gel vehicle in conjunction with the modification of the drug as a potentially faster drug delivery system.

Nonmetallic SERS-based biosensor for ultrasensitive and reproducible immunoassay of ferritin mediated by magnetic molybdenum disulfide nanoflowers and black phosphorus nanosheets

To improve the curability of cancer patients, it is essential to propose an early diagnosis technology with ultra-high sensitivity and reliable biocompatibility. Herein, a sophisticated nonmetallic SERS-based immunosensor, comprised by a MoS2 @Fe3O4 nanoflower-based immunoprobe with magnetism and a black phosphorus (BP) nanosheet-based immunosubstrate, was proposed for the specific in-situ monitoring of ferritin (FER). The sandwich immunosensor was endowed with an excellent SERS performance mainly ascribed to a synergistic chemical enhancement as well as an additional electrostatic adsorption effect, achieving a limit of detection down to 7.3 × 10−5 μg/mL. Particularly, all the Raman label, target FER, and anti-FER could be completely degraded within 70 min under visible light irradiation owing to the favorable photocatalytic activities of MoS2 and BP which could be then effectively separated and collected with the assistance of an external magnet. Such a recyclable nonmetallic immunosensor holds great potential and practicality in the clinical screening of cancer. [Display omitted]

Revealing Adsorption Mechanism of p-Mercaptobenzoic Acid with TiO2 Surfaces Using Electric Field-Enhanced Semiconductor SERS

p-Mercaptobenzoic acid (4-MBA) is a typical molecular probe for a surface-enhanced Raman scattering (SERS) study of the enhancement performance of semiconductor nanoparticles. Understanding the molecular adsorption mechanism of 4-MBA on a semiconductor surface is crucial to reveal the enhancement mechanism of semiconductor SERS. Herein, two types of submicrometer-sized TiO2 particles with amorphous (denoted as a-TiO2) and anatase structures (denoted as c-TiO2) were fabricated, and their potential as SERS-active substrates with high electric-field enhancement was explored based on the near-field scattering theory and finite-element method simulation. The electric field-enhanced semiconductor SERS provide a better vision for us to study the adsorption modes of molecules on the TiO2 surface. On this basis, adsorption behaviors of 4-MBA on a-TiO2 and c-TiO2 particles were systematically studied by the semiconductor SERS and density functional theory. The results demonstrated that the adsorption mechanism of 4-MBA with TiO2 surfaces is highly dependent on the exposure of acid sites of TiO2 surfaces. 4-MBA adsorbs preferentially on Brønsted acid sites of a-TiO2 through a carboxyl group, in contrast on Lewis acid sites of c-TiO2 through a sulfhydryl group. Furthermore, 4-MBA molecules may form multilayer adsorption on TiO2 surfaces through the hydrogen bond and/or π–π stacking interaction. Research results not only provide a new insight to re-evaluate the chemical enhancement mechanism for TiO2–4-MBA systems but also provide a theoretical guidance for the modification of TiO2 surface with organic molecules containing carboxyl and sulfhydryl groups.

Recyclable detection of gefitinib in clinical sample mediated by multifunctional Ag-anchored g-C3N4/MoS2 composite substrate

Surface-enhanced Raman scattering (SERS) technology enables to satisfy the increasing demand of clinical drug monitoring due to the superiority of fingerprint recognition, real-time response, and nondestructive collection. Here, a novel graphitic carbon nitride (g-C3N4)/ molybdenum disulfide (MoS2)/Ag composite substrate with a 3D surface structure was successfully developed for the recyclable detection of gefitinib in serum. Attributed to the uniform and dense “hotspots” on the shrubby active surfaces in conjunction with the potential synergistic chemical enhancement of g-C3N4/MoS2 heterosystem, a remarkable SERS sensitivity with an attractive enhancement factor value of 3.3 × 107 was demonstrated. Meanwhile, a type-II heterojunction between g-C3N4 and MoS2 enabled more efficient diffusion of photogenerated e−-h+ pairs assisted by the localized surface plasmon resonance of Ag NPs, which contributed to the reliable recyclable detection of gefitinib. The ultra-low limit of detection at 10−5 mg/mL and high recycling rates of gefitinib beyond 90% in serum were successfully realized. The results demonstrated the as-prepared SERS substrate has tremendous potential to be untilized for in-situ drug diagnostics.

TRANSFERSOMES AS NOVEL DRUG DELIVERY SYSTEM

Transdermal drug delivery appears to be most vital drug delivery system because of its merit over conventional systems. Transferosomes & the fundamental concept of transfersomes were launched by Gregor Cevc in the year 1991. The name means carrying body and is derived from the Latin word transferre, meaning to carry across and the Greek word soma, meaning a body. Novel drug delivery system aims to deliver the drug at a rate directed by need of body during the period of treatment and channel the active entity to the site of action. Transferosome is one of the novel vesicular drug delivery system which consists of phospholipids, surfactant and water for enhanced transdermal delivery. Transferosomes are able to reach intact deeper regions of the skin after topical drug administration while delivering higher concentrations of active substances making them a successful carrier for transdermal applications. These vesicular systems can deliver low as well as high molecular weight compounds. Targeted and controlled release formulations can also be prepared by transferosomes as it can accommodate drug molecules with wide range of solubility. Various strategies can be used to augment the transdermal delivery which includes iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, & vesicular system (liposomes, niosomes, elastic liposomes such as ethosomes & transfersomes). It exists as an ultra-deformable complex having a hydrated core surrounded by a complex layer of lipid. It penetrates the stratum corneum by either intracellular route or the transcellular route by the generation of osmotic gradient. Advantages of Transferosomes are wide range of solubilities, better penetration, biocompatible and biodegradable etc. Disadvantages of Transferosomes are oxidative degradation, expensive, etc. The transfersomes were formulated by the conventional rotary evaporation sonication method. Transferosomes can be applied in controlled release, transportation of large molecular weight compounds, target delivery to peripheral subcutaneous tissues, transdermal immunization etc.

Simulating the Detection of Dioxin-like Pollutants with 2D Surface-Enhanced Raman Spectroscopy Using h-BNC Substrates

The ability of 2D hybrid structures formed by boron, nitrogen and carbon atoms (h-BNCs) to act as potential substrates for the surface-enhanced Raman spectroscopy (SERS) detection of dioxin-like pollutants is theoretically analyzed. The strong confinement and high tunability of the electromagnetic response of the carbon nanostructures embedded within the h-BNC sheets point out that these hybrid structures could be promising for applications in optical spectroscopies, such as SERS. In this work, two model dioxin-like pollutants, TCDD and TCDF, and a model h-BNC surface composed of a carbon nanodisk of ninety-six atoms surrounded by a string of borazine rings, BNC96, are used to simulate the adsorption complexes and the static and pre-resonance Raman spectra of the adsorbed molecules. A high affinity of BNC96 for these pollutants is reflected by the large interaction energies obtained for the most stable stacking complexes, with dispersion being the most important contribution to their stability. The strong vibrational coupling of some active modes of TCDF and, specially, of TCDD causes the static Raman spectra to show a ”pure” chemical enhancement of one order of magnitude. On the other hand, due to the strong electromagnetic response of BNC96, confined within the carbon nanodisk, the pre-resonance Raman spectra obtained for TCDD and TCDF display large enhancement factors of 108 and 107, respectively. Promisingly, laser excitation wavelengths commonly used in SERS experiments also induce significant Raman enhancements of around 104 for the TCDD and TCDF signals. Both the strong confinement of the electromagnetic response within the carbon domains and the high modulation of the resonance wavelengths in the visible and/or UV region in h-BNCs should lead to a higher sensitivity than that of graphene and white graphene parent structures, thus overcoming one of the main disadvantages of using 2D substrates for SERS applications.

Repair of corroded steel bridge girder end regions using steel, concrete, UHPC and GFRP repair systems

Practical means of affecting in situ repair of corrosion-induced section loss of steel bridge girders at their supports are compared. Potential repair strategies are reviewed leading to large-scale experimental evaluation of four methods of repair: conventional bolted steel repair, encasement in conventional reinforced concrete (RC), encasement in ultra-high performance concrete (UHPC), and reinforcement with externally bonded fiber-reinforced polymer (FRP) plates and sections. Modified W24x55 girders representing half-scale 1400 mm deep plate girders were used. Section loss mimicking typically-observed severe corrosion was machined into the girder ends. Monotonic load tests to failure were conducted on the repaired girders and companion tests were conducted of identical specimens subject first to one million cycles of fatigue loading before being loaded to failure. Results indicate the efficacy of conventional bolted steel repair methods. UHPC and RC encasement was also shown to perform well and may be suited to certain scenarios. Despite extensive surface preparation and chemical enhancement, the bond of the FRP system to the damaged substrate steel was poor; this system is not an appropriate repair method for this damage scenario.

Skin penetration of caffeine from commercial eye creams and eye creams designed and optimized based on Hansen solubility parameters

Computer-aided formulation design can streamline and speed up product development. In this study, ingredient screening and optimizing software, Formulating for Efficacy® (FFE), was used to design and optimize creams for the topical delivery of caffeine. FFE was set up to optimize lipophilic active ingredients, therefore, this study challenged the program’s capabilities. The effect of two chemical penetration enhancers, including dimethyl isosorbide (DMI) and ethoxydiglycol (EDG), were studied based on their favorable Hansen Solubility Parameter physicochemical input parameters for the skin delivery of caffeine in the FFE® software application. Four oil-in-water emulsions containing 2% caffeine were formulated, one without a chemical penetration enhancer, one with five percent of DMI, one with five percent of EDG, and one with 2.5% of DMI and EDG each (DMI + EDG). Additionally, three commercial products were used as reference products. The cumulative amount of caffeine released and permeated, and the flux across Strat-M® membranes were determined using Franz diffusion cells. The eye creams had skin-compatible pH, excellent spreadability for the application area, were opaque emulsions with 14–17 μm droplet size, and were stable at 25 °C for 6 months. All four eye creams formulated released over 85% of caffeine in 24 h, outperforming the commercial products. DMI + EDG cream provided the highest permeation in vitro in 24 h, which was significantly higher than the commercial products (p < 0.05). FFE proved to be a valuable and quick tool to aid in the topical delivery of caffeine.

Benzonatate as a local anesthetic.

Benzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade. Benzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis. Benzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations. This study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations.

Recognition of dipole-induced electric field in 2D materials for surface-enhanced Raman scattering.

The application of two-dimensional (2D) materials, including metallic graphene, semiconducting transition metal dichalcogenides, and insulating hexagonal boron nitride (h-BN) for surface-enhancement Raman spectroscopy has attracted extensive research interest. This article provides a critical overview of the recent developments in surface-enhanced Raman spectroscopy using 2D materials. By re-examining the relationship between the lattice structure and Raman enhancement characteristics, including vibration selectivity and thickness dependence, we highlight the important role of dipoles in the chemical enhancement of 2D materials.