Micro and Nanosystems - Volume 13, Issue 3, 2021

Background: Self-assembled drug delivery systems are of much interest since they can be produced by simple low cost and solvent-free procedures. Pharmacosomes are supramolecularstructured nanocarriers with benefits for drug stability and targeting delivery. Amphotericin B (AmB) still remains an important agent for the treatment of invasive mold infections, e.g invasive aspergillosis, although the challenge for new formulations is still prevailing due to high rates of toxicity. Objective: We have previously reported the incorporation of AmB into 12-hydroxystearic acid lipidbased microtubes (MTs) for topical use, herein we report the ability of AmB-MTs to self-assemble into vesicles upon dilution. Methods: AmB-MTs with different drug concentrations (1, 3, 5 mg/ml) were prepared, and size determination was carried out for different dilutions. Morphology was evaluated by microscopy. In vitro cytotoxicity was evaluated in Vero cells and in vitro activity against Aspergillus fumigatus and Aspergillus flavus was assessed. Results: AmB-MTs closed upon dilution to form vesicles ranging from 200 nm to 1μm. AmB MIC (Minimum inhibitory concentration) for both Aspergillus species was 0.0625 and 0.125 μg/ml for dispersion and reconstituted lyophilized, respectively. Conclusion: AmB pharmacosome-like vesicles are smaller structures than MTs may thus be favourable for other delivery routes. We assume that this kind of pharmacosomes-like carrier is a promising model for the obtention of new vesicular carriers based on lipid MTs.

Aims: The administration of antitumor 5-Fluorouracil (5-FU) into the human body is generally accomplished via a central venous catheter that is prone to degradation when it comes in contact with bodily fluids or aggressive drugs such as 5-Fu. Therefore, degradation could be reduced by applying protective coatings onto the internal and/or external surfaces of the catheters. Objective: Graphene and silica materials could be promising coating materials because of their low reactivity and antimicrobial properties. The mechanisms of interaction between the carrier and the drug are based on surface chemistry related phenomena. Understanding the physicochemical features of the surfaces is a fundamental step to describe and predict the strength of these interactions and may result in controlled adsorption and release processes. Methods: Computational DFT methods can provide an important aspect by providing atomistic details of the drug adsorbed on the surfaces through molecular modeling. Results: DFT calculations of the binding energy, charge exchange and orbital population of 5-FU adsorbed on graphene and silica materials confirmed weak interactions between the drug and the solid surfaces that could favor desorption during the drug delivery. Graphene and silica surfaces do not react with the 5-FU molecule behaving as inert materials and the drug does not suffer from degradation nor alter its structure during adsorption on both the materials. Conclusion: These characteristics, in addition to biocompatibility and antimicrobial properties, suggest that graphene and silica could be used as promising internal/external coating materials for biomedical applications.

Acne is a chronic disease associated with the pilosebaceous unit and is affected by Propionibacterium acnes bacteria. Approximately 95% of people worldwide suffer from acne in their life span with a higher prevalence among teenagers (esp. boys). Conventional strategies incorporating antibiotics, steroids, hormones, etc. are recommended orally, systemically, or topically, employed for the treatment of acne but with various side effects (itching, scaling, redness, etc.) and are no more commercially accepted. The literature has been collected using various search engines google scholar, PubMed, science direct, etc. The review highlights the history of acne, its pathophysiology, developmental factors, various treatment evolutions strategies ranging from conventional to novel approach eradicating the secondary effects with enhanced efficacy and safety profile. We discussed various nanotechnological carriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, microsponges and other nanoscale formulations), which are formulated in the last decade for the effective treatment of acne. Patent literature and marketed formulations are included in the last sections. The encapsulation efficiency of anti-acne drugs in different nanocarriers improves the efficacy as well as minimizes the side effects of the drug. These carriers showed better bioavailability as well as better penetration effects even to the pilosebaceous unit of the skin. Tolerance can be improved by increasing the concentration of anti-acne drugs in the nano-carrier formulation. Conventional treatment strategies for acne had some limitations like scaling, itching, and inflammation which can be overcome by nano-formulations, which exhibit better efficacy. At present, various nano-technological carriers are being used potentially for the treatment of acne. These nano-formulations are also associated with some limitations like drug entrapment, stability issues, but these will be overcome in the upcoming years as long as the research is being continued in this area.

Background: For higher-order multiplications, a huge number of adders or compressors are used to perform the addition of the partial products. Objective: Hence, the area and the propagation delay will increase. Researchers are trying to reduce the number of additions of partial products. Methods: In this paper, different modified compressors have been proposed and based on these compressors, 16x16-bit binary multiplier has been discussed. Results: The proposed design provides better area, power consumption, critical path delay and less number of transistor counts when compared to other designs using the conventional compressors. Here, the proposed method has been used in the Wallace tree multiplier or Dadda tree multiplier. The compressor used here has been implemented using Microwind DSCH 3.8 lite. Conclusion: The modified compressor makes the multiplier faster and reduces the number of addition of partial products.

Background: A relatively narrow LSPR peak and a strong interband transition ranging around 800 nm make Al a strongly plasmonic active material. Usually, Al nanoparticles are preferred for UV-plasmonic as the SPR of small size Al nanoparticles is located in the deep UV-UV region of the optical spectrum. This paper focused on tuning the LSPR of Al nanostructure towards the infrared region by coating the Au layer. The proposed structure has Au as the outer layer, which prevents further oxidation of Al nanostructure. Methods: The Finite Difference Time Domain (FDTD) and Plasmon Hybridization Theory has been used to evaluate the LSPR and field enhancement of single and dimer Al-Al2O3-Au MDM nanostructure. Results: It is observed that the resonance mode shows dependence on the thickness of the Al2O3 layer and also on the composition of the nanostructure. The Au layered MDM nanostructure shows two peaks of equal intensities simultaneously in UV and visible region tuned to the NIR region. The extinction spectra and electric field distribution profiles of dimer nanoparticles are compared with the monomer to reveal the extent of coupling. The dimer configuration shows higher field enhancement ~10⁷ at 1049 nm. By optimizing the thickness of the dielectric layer, the MDM nanostructure can be used over the UV-visible-NIR region. Conclusion: The LSPR peak shows dependence on the thickness of the dielectric layer and also on the composition of the nanostructure. It has been observed that optimization of size and thickness of the dielectric layer can provide two peaks of equal intensities in the UV and Visible region, which are advantageous for many applications. The electric field distribution profiles of dimer MDM nanostructure enhanced the field by ∼10⁷ in visible and NIR region showing its potential towards SERS substrate. The results of this study will provide valuable information for the optimization of LSPR of Al-Al2O3- Au MDM nanostructure to have high field enhancement.

Aims: AA7076 is a well-defined alloy for its excellent physical and mechanical properties such as high strength, toughness, and low density. To meet the requirements of the automobile and aerospace industry, the properties of AA7076 alloy have to be improved by reinforcing nano-sized graphene amine particles. Objectives: The aim of this study is to synthesize and characterize the AA7076 alloy reinforced with graphene nanofillers for different structural engineering applications. Methods: In this present work, nano-sized graphene amine particles were added and dispersed homogeneously using a motorized stir casting technique. AA7076/graphene amine composites were prepared by varying wt.% percent of graphene amine reinforcement particles (0.5, 0.75, 1, and 1.25 wt.% (weight-percentage)). Results: The SEM micrographs reveal the homogeneous distribution of graphene amine reinforcements along the grain boundaries of the AA7076 matrix material. The experimental test results showed that with the addition of graphene amine reinforcements, the mechanical properties of the AA7076/graphene amine composites improved as compared to the AA7076 matrix material. Conclusion: The composite with 1 wt.% graphene amine showed higher strength and hardness as compared to other reinforcements.

Background: Moxifloxacin is a BCS class I drug used in the treatment of bacterial conjunctivitis and keratitis. Despite its high water solubility, it possesses limited bioavailability due to anatomical and physiological constraints associated with the eyes, which require multiple administrations to achieve a therapeutic effect. Objective: In order to prolong drug release and to improve antibacterial efficacy for the treatment of bacterial keratitis and conjunctivitis, moxifloxacin-loaded nanoemulsion was developed. Methods: The concentration of oil (oleic acid), a surfactant (tween 80), and a cosurfactant (propylene glycol) were optimized by employing a 3-level 2-factorial design of the experiment for the development of nanoemulsion. The developed nanoemulsion was characterized by particle size distribution, viscosity, refractive index, pH, drug content and release, Transmission Electron Microscopy (TEM), and antibacterial study. The compatibility of the drug with the excipients was accessed by Fourier Transform Infrared Spectroscopy (FTIR). Results: The average globule size was found to be 198.20 nm. The TEM study revealed that the globules were nearly spherical and well-distributed. In vitro drug release profile of the nanoemulsion showed a sustained drug release (60.12% at the end of 6 h) compared to drug solution, with complete drug released within 2 h. The antibacterial effectiveness of the drug-loaded nanoemulsion improved against S. aureus compared with the marketed formulation. Conclusion: The formulated sustained-release nanoemulsion could be a promising alternative to eye drops with improved patient compliance by minimizing dosing frequency with improved antibacterial activity.

Background: HQ is used for hyper-pigmentation treatment using conventional creams and gels. These formulations show various disadvantages like poor skin permeation, allergic reactions, and repeated use and decreasing patient compliance. Objectives: The present work involved formulation, statistical optimization, and characterization of Nanostructured Lipid Carriers (NLCs) for efficient topical delivery of hydroquinone (HQ) for hyperpigmentation treatment. Methods: The NLCs were optimized exploring Box–Behnken Design (BBD) using three independent variables and two dependent variables. Formulation having the minimum size and maximum drug entrapment was considered as optimized formulation. The optimized formulation was evaluated for drug release followed by its freeze-drying. The freeze-dried formulation was subjected to Differential Scanning Calorimetry (DSC) analysis, X-Ray Diffraction (XRD) analysis, and Fourier Transform-Infrared spectroscopy (FT-IR) analysis. Furthermore, NLCs based gel was prepared by using Carbopol 934 as a gelling agent. NLCs based gel was evaluated for skin permeation, skin retention, and skin distribution (through confocal microscopic analysis) using pig ear skin. Results: Optimized NLCs showed smaller particle size [(271.9 ± 9) nm], high drug entrapment [(66.4 ± 1.2) %], tolerable polydispersity index (PDI) (0.221 ± 0.012), and zeta potential [(-25.9 ± 1.2) mV]. The FT-IR analysis revealed excellent compatibility between HQ and other excipients. The Carbopol 934 gel containing NLCs showed high transdermal flux [(163 ± 16.2) μg/cm²/h], permeability coefficient (0.0326 ± 0.0016), and skin permeation enhancement ratio (3.7 ± 0.4) compared to marketed cream of HQ. The results of confocal microscopic (CLSM) analysis revealed the accumulation of optimized NLCs in the lower epidermal layers of skin. Conclusion: NLCs based gel was considered effective in the topical delivery of HQ to treat hyperpigmentation due to high skin permeation, skin retention, and prolonged release of HQ.

Aims: The semiconductor technology has a great impact on consistent growth in the Very-Large- Scale Integrated (VLSI) devices. The transistor size has been scaled down from micron to submicron and towards the nanometer regime in the past 30 years due to technological advancements. The most reliable solid-state device is Metal-Oxide-Semiconductor Field Effect Transistor (MOSFET) but this rapid decrease in the device dimensions with the advent of Moore's law follows several problems, such as Short Channel Effects (SCE's) and Hot Carrier Effects. The channel becomes too small at short channel effects that necessitate the analysis of the optimum device designs, in particular in the operating conditions. The charge-sheet model that can quickly analyze a long-channel device, currently in the subthreshold to saturation regime without any discontinuity, turns out to be inappropriate at reduced channel size.

Objectives: At the nano-scaling of the device, since the accumulation layer thickness is comparable to the device, the assumption of the channel as a thin sheet of charge vanishes. Though the depletion layers or zone are the regions of the absentia of charges mostly, the existence affects the device behavior and the channel thickness. Therefore, channel thickness modeling becomes essential at various bias conditions to define the specifics of device operation and the channel dependence of the structural parameters. In this work, the objective is to develop an analytical model and numerical analysis of the Cylindrical Surrounding Double-Gate (CSDG) MOSFET, including the thickness, derived based on the formation of depletion depth to analyze the device performance at reducing dimensions.

Methods: The analysis is built upon the device's physical and electrical parameters, such as capacitance, electric field, thickness, threshold voltage, effective channel dimensions, drain current, are considered in this research. The depletion region in a MOSFET structure accounts for the inclusion of the source and drain depletion regions, divided primarily into three separate sub-regions as a junction between the diffused source/drain and the substrate depletion under the channel and by region induced by lateral source and drain diffusion. The condition of a planar MOSFET in channel formation, i.e., for strong inversion, and when VGS > VTH has been considered for this mathematical analysis.

Results: The computed results of device thickness and depending parameters for a planar MOSFET and the CSDG MOSFET have been obtained. Based on this analysis, the silicon thickness of the typical CSDG MOSFET computed is 180 nm, 281 nm, and 327 nm at VDS 0.2 V, 0.8 V, and 1.2 V, respectively. The achieved results, through the thickness modeling proposed in this work, show that nanoscale CSDG MOSFET can be deployed for the improvements in the device performance and novel design modifications.

Conclusion: The analysis presented in this work significantly contributes to understanding the dependence of semiconductor thickness in CSDG MOSFET and serves as a guide for future modifications in the structure for the device compactness.

Background: The current treatments of leishmaniosis are far from ideal since they require the administration of toxic and poorly tolerated drugs that still fail to treat the intracellular infection. Micro-particles are very promising drug carriers for leishmaniosis treatment, considering the involved parasites’ life cycle and the pharmacokinetics of micro-particles. Objective: The aim of this study is to develop a novel formulation of Nystatin (Nys) that could be administered systemically and might be used for therapy of Leishmaniosis. Methods: Nys microspheres were formulated using albumin as a carrier by spray drying for the preparation of microspheres for intravenous administration. Nys microspheres were characterized morphologically and evaluated for particle size, product yield, encapsulation efficiency, and drug-polymer interaction. Anti-Leishmanial activity against Leishmania tropica was tested and the microspheres’ phagocytosis by murine macrophages was investigated. An in vitro hemolysis study was carried out for the novel formulation and for the free Nys. Results: The average size of microspheres was found to be less than 5 μm. Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared spectroscopy (FTIR) confirmed no significant interactions between albumin and Nys. The anti-leishmanial activity of Nys microspheres was higher than that for free Nys with an IC50 value of (18.1 μg/mL). Uptake study in murine macrophage confirmed the targetability of the prepared microspheres. The in vitro hemolysis study indicated reduced hemolysis and suitability of the microspheres for parenteral administration. Conclusion: Spray drying was used successfully to prepare highly loaded Nys microspheres with high anti-leishmanial activity and less hemolysis effect.

Background: At present, the main problems of Micro-Electro-Mechanical Systems (MEMS) based temperature detector are the narrow range of temperature detection and difficulty in the measurement of high temperature. Besides, MEMS devices have different response characteristics for various surrounding temperature in the petrochemical and metallurgy application fields with hightemperature and harsh conditions. To evaluate the performance stability of the high-temperature MEMS devices, the real-time temperature measurement is necessary. Objective: A Schottky temperature detector based on the metal/n-ZnO/n-Si structures is designed to measure high temperature (523∼873K) for MEMS devices with a large temperature range. Methods: By using the Finite Element Method (FEM), three different work function metals (Cu, Ni and Pt) contacting the n-ZnO were investigated to realize Schottky. At room temperature (298K) and high temperature (523∼873K), the current densities with various bias voltages (J-V) were studied. Results: The simulation results show that the high-temperature response power consumption of three Schottky detectors of Cu, Ni and Pt decreases successively, which is 1.16 mW, 63.63 μW and 0.14 μW. The response temperature sensitivities of 6.35 μA/K, 0.78 μA/K, and 2.29 nA/K are achieved. Conclusion: The Cu/n-ZnO/n-Si Schottky structure could be used as a high-temperature detector (523∼873K) for the high-temperature MEMS devices. It has a large temperature range (350K) and a high response sensitivity of 6.35 μA/K. Compared with the traditional devices, the Cu/n-ZnO/n-Si Schottky structure-based temperature detector has a low energy consumption of 1.16 mW, having potential applications in the high-temperature measurement of the MEMS devices.

Background: Glimepiride is a third-generation, oral anti-diabetic sulfonylurea drug, generally recommended for the treatment of type–II diabetes. A biocompatible polymer, Eudragit RS 100 is widely used for the preparation of targeted and time-controlled release of drugs. Glimepiride is encapsulated using Eudragit RS 100 for sustained release delivery. Objective: To develop sustained release microparticles of Glimepiride using microreactor technology to reduce the dosing frequency. Methods: Microreactor precipitation method was used to develop sustained release microparticles of Glimepiride. Plackett-Burman design was employed for the optimization of all the parameters including the inner diameter of silicon tubing, the flow rate of solvent as well as antisolvent, length of tubing and concentration of polymer, etc. Microparticles prepared were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, Scanning electron microscopy and in vitro drug release as well as release kinetics study. Results: Placket Burman design was found to be effective for comparing more than two parameters at a time and showed the effect of parameters on design. The parameters A, B, C, D, E and J synergistically affected the encapsulation efficiency. FE-SEM demonstrated the smooth and spherical nature of particles. Fourier transformed infrared spectroscopy showed the absence of chemical interaction between polymer and drug; X-ray diffraction results showed the decrease in crystallinity of pure drug when it was transformed into encapsulated drug-loaded microparticles. The sustained drug release was observed for 12 h. Conclusion: Prepared Glimepiride loaded sustained release microparticles followed the first-order release kinetics. The developed formulation could reduce dose frequency and improve patient compliance.

Aim: Computation of loss factors for one-bit RF MEMS switch over Ku, K and Ka-band for two different insulating substrates. Objective: Numerical investigation of return loss, insertion loss, isolation loss are computed under both actuated and unactuated states for two different insulating substrates of the 1-bit RF MEMS switch, and corresponding up and down-capacitances are obtained. Methods: The unique characteristics of a 1-bit RF MEMS switch of providing higher return loss under both actuated and unactuated states and also of isolation loss with negligible insertion loss makes it as a prime candidate for phase shifter application. This is presented in this manuscript with a keen focus on improvement capability by changing transmission line width, and also of overlap area; where dielectric constant of the substrate also plays a vital role. Results: The present work exhibits very low down-capacitance over the spectrum whereas a considerable amount of up-capacitance. Also when overall performance in terms of all loss parameters are considered, switch provides very low insertion loss, good return loss under actuated state and standard isolation loss. Conclusion: Reduction of transmission line width of about 33% improved the performance of the switch by increasing isolation loss. Isolation loss of -40 dB is obtained at actuated condition in higher microwave spectra for SiO2 at higher overlap area. Down capacitance of ∼ 1dB is obtained which is novel as compared with other published literature. Moreover, a better combination of both return loss, isolation loss and insertion loss are reported in this present work compared with all other published data so far.

Aim: Establish the efficient footprint size, i.e., the total substrate width of photonic waveguides (Ridge, Rib, and Slot) under the fundamental mode propagation constraints. Objective: By varying the total substrate width for all photonic waveguides (Ridge, Rib, and Slot) with respect to four major waveguide parameters, namely effective refractive index, propagation loss, propagation length, and confinement percentage, the converged values of these waveguide parameters have to be obtained. Methods: The Finite Element Method (FEM) based simulations, using the COMSOL Multiphysics, have been used to study the modal characteristics of photonic waveguides to achieve their efficient footprint size. Results: The total substrate widths have been obtained for all four parameters and considering the impact of all these waveguide parameters simultaneously, the efficient total substrate width has been recognized as 2500 nm, 4000 nm, and 3000 nm, respectively, for Ridge, Rib, and Slot waveguides. Conclusion: The efficient waveguide footprints, i.e., the total substrate widths for the three photonic waveguides, namely Ridge, Rib and Slot waveguides have been established.