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  • Open access
  • 32 Reads
Co-axial wet-spun fibers: an innovative strategy for chronic wound healing applications

Chronic wounds (CW) are a worldwide concern, causing serious strives on the health and quality of patients’ life. In CW, human neutrophil elastase (HNE) enzyme gets highly expressed during inflammation, reaching abnormally elevated concentrations. Additionally, prevalence of Staphylococcus aureus-induced infections remains very high and difficult to treat. Considering these phenomena, a drug delivery system made of co-axial wet-spun fibers, loaded with the tetrapeptide Ala-Ala-Pro-Val (AAPV, a known inhibitor of HNE activity) and N-carboxymethyl chitosan (NCMC, responsive to neutral-basic pH’s, characteristic of CW and endowed with antibacterial features), was proposed.

AAPV was synthesized by solid-phase peptide synthesis, whereas NCMC was synthesized from low molecular weight chitosan in a chloroacetic acid mixture. HNE inhibition tests were conducted to establish the AAPV IC50 in 1.50 µg/mL and the NCMC minimum bactericidal concentration (MBC) against Staphylococcus aureus in 6.40 mg/mL. These determinations were used to establish fiber loading amounts. Core-shell structures were produced with 10% w/v polycaprolactone (PCL) at the core and 2% w/v sodium alginate (SA) solution at the shell. NCMC was mixed with SA at 2×MBC so neutral-basic pH-triggered solubility (characteristic of CW) would allow pores to be opened in the outer layer for accessing the core, where AAPV was combined with PCL.

Fourier-transform infrared spectroscopy and brightfield microscopy were used to confirm the presence of the four components on the fibers and the co-axial architecture, respectively. Fibers presented maximum elongations of over 100%. Release kinetics studies conducted via UV-visible absorption spectroscopy mapped NCMC liberation overtime but were uncapable of detecting AAPV, since polymer degradation masked AAPV absorption peaks. Time-kill kinetics studies against S. aureus demonstrated the effectiveness of NCMC in eliminating this bacterium, particularly after 6 h of incubation. On its turn, AAPV guaranteed HNE inhibition. Data demonstrated the potential of SA-NCMC-PCL-AAPV co-axial systems to work as stepwise, pH-triggered delivery platforms.

  • Open access
  • 42 Reads
Influence of agricultural activity on the surface climate of New Delta of Egypt using the RegCM4

The present study aims to examine the influence of a cropped area (of New Delta in Egypt) on the temperature extremes (Tmax and Tmin), total surface precipitation (Pr), and potential evapotranspiration (PET; as an important variable in the water cycle) using a regional climate model (RegCM4). The RegCM4 was downscaled by the MPI-ESM-MR (as the lateral boundary condition; LBC) over the Middle East and North Africa (MENA) with 50 km grid spacing and then nested over Egypt with 20 km grid spacing. After that, the RegCM4 was evaluated with respect to an observational dataset. To consider the effect of the cropped area, two experiments were conducted: one doesn’t include the cropped area (CTRL) and the other one considers the cropped area (EXP). The two experiments were integrated from 1980 to 2100 considering the future scenario representative concentration pathway 4.5 (RCP45). The results showed that the cropped area induces a reduction in both Tmax and Tmin (by 0.5 – 1.5ºC) as well as a reduction in PET (by 0.2 mm day-1). Furthermore, there was no notable change in the simulated Pr. In conclusion, the RegCM4 is considered a useful tool to examine the possible effects associated with the cropped area. Also, considering more LBC is necessary to account for the uncertainty associated with the atmospheric forcing.

  • Open access
  • 41 Reads
Synthesis of Target-directed Nanogel Carrier with Glycopolymers and Their Application to Immunotherapy
Published: 01 December 2022 by MDPI in The 3rd International Electronic Conference on Applied Sciences session Posters

Immunotherapy to induces antigen-specific immunity is expected to be an effective and safe treatment for cancer and infectious diseases, and induction of cytotoxic T lymphocytes (CTL) is particular important to treat these diseases. For effective CTL activation, antigen-presenting cells (APC) such as macrophages and dendritic cells must take up antigenic proteins/antigen peptides, trough degradation them intracellularly, and present the generated peptide fragments on MHC class I molecules. Although various antigen administration methods have been studied to induce CTL efficiently, conventional techniques have not been sufficiently effective. The main reasons are low translocation of their antigens to APC and protein instability during in vivo delivery. In this study, we prepared a core-shell mannose-installed nanogel with a suitable aqueous environment for a protein stabilization that can be active-targeted to dendritic cells in vivo. Targeting of the nanogel to dendritic cells with mannose receptors was confirmed by aggregation inhibition experiments of silica particles mimicking nanogel structures. For higher sensitivity, gold nanoparticle grafted with mannose-glycopolymers was synthesized, and the specific binding to lectin was analyzed from the surface plasmon changes. In addition, inhibition experiments were also conducted to investigate the binding mode in more detail. Mannose-type glycan block copolymers (pManEMA-b-pMAA, Man) were synthesized by RAFT polymerization using the monomer consisting of D(+)-Mannose and 2-hydroxyethyl methacrylate (ManEMA) and methacrylic acid (MAA). Next, the surface of hydrophilic silica nanoparticle (SiNP) was modified with pManEMA-b -pMAA via a silane coupling agent having an amino group at the end. The specificity of mannose presenting SiNP (SiNP-Man) to the receptor protein was evaluated from the inhibition experiment by the addition of free mannose as an inhibitor. The structure of the synthesized glycopolymers was confirmed by 1H-NMR spectra and GPC measurements. Competitive inhibition of SiNP-Man aggregation by lectin was confirmed by the addition of free mannose as an inhibitor. When concanavalin A (ConA), mannose specific lectin, was added to the SiNP-Man solution, particles aggregated due to the specific interaction at the low inhibitor. However, when excess amount of inhibitor was added, the binding site of the lectin was competitively suppressed and the particles did not aggregate. These results confirm the active target property of the mannose-modified nanoparticles.

  • Open access
  • 71 Reads
The importance of nanosystems in antipsychotic drugs brain targeting

Orally administered antipsychotic drugs are the first line treatment in the management of psychotic disorders, that affect millions of people globally and have a tremendous impact on patient and family lives, such as schizophrenia and bipolar disorder. Nevertheless, adverse drug reactions hinder clinical outcomes, resulting in patient non-compliance. The design and implementation of adequate formulation strategies for enhancing drug delivery and targeting to the brain has been a significant challenge, mainly due to the restrictive properties of the blood-brain barrier. However, recent pharmacokinetic and pharmacodynamic in vivo assays confirmed that there is evidence of the advantage of the intranasal route, when compared to oral and intravenous administration, as it allows the possibility of direct nose-to-brain transport, via neuronal olfactory and trigeminal pathways, reducing systemic side effects and maximizing therapeutic outcomes. In addition, the formulation of polymeric and solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, nanoemulgels, nanosuspensions, niosomes, Spanlastics and polymeric mixed micelles is a promising approach, since they have a reduced particle size, ideal for nose-to-brain delivery, stability, high encapsulation efficiency, enhanced drug solubility, and drug protection from enzymatic degradation. Nevertheless, it is essential to continue research in this field, conducting more long-term studies with greater uniformity, so that the true potential of these formulations can be assessed and a transposition into the pharmaceutical industry is someday possible.

  • Open access
  • 37 Reads
Brain targeting of antidepressant and anxiolytic drugs

Depression and anxiety are high incidence and debilitating psychiatric disorders, usually treated by antidepressant or anxiolytic drug administration (respectively). Nevertheless, this treatment is usually done through the oral route, but the low permeability of the blood-brain barrier, that has the many functions of being a barrier to prevent the entry of external substances into the brain, reduces the amount of drug that will be able to reach the brain, also reducing, consequently, therapeutic efficacy. Which is why new solutions have been tried to make these treatments more effective, safer, and faster. To overcome this obstacle, in the articles analyzed in this work three main strategies were used to improve brain drug targeting: the intranasal route of administration, which allows the drug to be directly transported to the brain by neuronal pathways (olfactory and trigeminal nerves), bypassing the blood-brain barrier and avoiding hepatic and gastrointestinal metabolism; the use of nanosystems for drug encapsulation, including polymeric and lipidic nanoparticles, nanometric emulsions and nanogels; and drug molecule functionalization, by the attachment of ligands such as peptides and polymers. Pharmacokinetic and pharmacodynamic results showed that intranasal administration can be more efficient in brain targeting than other routes (such as intravenous or oral administration), as well as the use of nanoformulations and drug functionalization, which are also quite beneficial in increasing brain drug bioavailability.

  • Open access
  • 35 Reads
Exploiting the power of decellularized extracellular matrix for periodontal tissue regeneration

Periodontitis is a worldwide prevalent infectious disease that causes the destruction of periodontal tissues and can lead ultimately to tooth loss. The goal of periodontal treatment is to control the infection and reconstruct the structure and function of all periodontal tissues, including cementum, periodontal ligament fibers and alveolar bone. However, most of the treatments, such as the use of membranes and bone grafts, lack bioactive signals that accelerate the process of tissue regeneration and cannot repair the attachment of periodontal tissues to teeth, leading to tooth loss. Therefore, it is imperative to exploit alternative strategies to repair the structure and function of all periodontal tissues.
Decellularized extracellular matrix (dECM) has been proven to be a promising biomaterial by providing a suitable microenvironment to support cell proliferation and differentiation.
We explored dECM-derived scaffolds, such as sponges and electrospun nanofibers, to recreate the cell niche of periodontal tissues. Our findings demonstrated that incorporation of dECM derived from periodontal ligament stem cells (PDLSC) promoted significant cell proliferation and enhanced osteogenic/periodontal differentiation of PDLSCs.
Overall, dECM-scaffolds have the potential to be used as novel ‘off-the-shelf’ biomaterials, providing a biomimetic microenvironment that may contribute to improve health care of patients suffering with periodontal diseases.

  • Open access
  • 29 Reads
Directional hemispherical reflectance as a quick method for analysis of degradation processes in commercial effervescent tablets
Published: 01 December 2022 by MDPI in The 3rd International Electronic Conference on Applied Sciences session Posters

Background: The degradation of active pharmaceutical ingredients (APIs) and the subsequent formation of degradation products affect the pharmaceutical quality of a medicinal product. Therefore, quick and effective detection of adverse changes occurring in a medicinal product is very important. The aim of the present study was to assess the total directional hemispherical reflectance (THR) of effervescent tablets containing magnesium and vitamin B6 during storage at ambient conditions.

Methods: The expired (n=20; expiration date 04.2021) and unexpired (n=20; expiration 03.2024) tablets were analyzed. The measurements of THR were performed with the use of SOC-410 Directional Hemispherical Reflectometer (USA) within seven wavelength bands (from 335 nm to 2500 nm). For each tablet, 3 measurements were done. The study was funded within the project PCN-1-058/K/2/O.

Results: The mean THR was significantly higher within the ranges of 400-540 nm, 480-600, 590-720, and 1000-1700 for the unexpired effervescent tablets compared to expired tablets (p<0.001). In turn, a significantly higher value of THR for the range of 700-1100 nm, and 1700-2500 nm was observed for expired tablets than for unexpired tablets (p<0.001). Surprisingly, we have observed significant differences in mean THR between the top side and the bottom side of tablets.

Conclusions: The measurement of THR may be a rapid test for detecting adverse physicochemical changes in these tablets and can be used for a further detailed evaluation of API and related degradation products.

  • Open access
  • 22 Reads
Effects of guanidinium and cesium addition to CH3NH3PbI3 perovskite photovoltaic devices
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Although silicon is the most common solar cell material, the fabrication process is complicated and expensive. In contrast, the CH3NH3PbI3 (MAPbI3) perovskite compound have tunable band gaps and easy fabrication process. However, MAPbI3 compounds are unstable in air due to the migration of CH3NH3 (MA). MAPbI3 crystals are known to be able to control their electronic states by the addition of other cations and anions, and this could be used to improve the stability of the perovskite photovoltaic devices. The purpose of the present work is to investigate the effects of addition of guanidinium C(NH2)3 (GA) and cesium (Cs) on MAPbI3 perovskite solar cells. The addition of GA/Cs and the insertion of decaphenylpentasilane between the perovskite and hole transport layer improved the external quantum efficiency and short-circuit current density, and the conversion efficiencies were stable. First principles calculations on the density of states and band structures showed reduction of the total energy by the GA addition.

  • Open access
  • 42 Reads
Thermoelectric metal oxides with reduced graphene oxide

New power generation strategies based on clean and sustainable energy sources are needed due to the exponentially increasing energy demands of the world. Thermoelectric (TE) conversion of widely distributed waste heat can be proposed as an alternative route to convert thermal or solar energy into electric power economically.

Chalcogenides or skutterudites has higher figure of merit ZT in comparison to oxide materials but they are toxic and have high cost. At the same time, there is current interest for metal oxides as high-temperature TEs in the energy-harvesting sectors due to high chemical robustness and low toxicity. Driven by a need to improve TE performance of n-type oxides, ceramics and composites based on donor-doped SrTiO3 are considered as a promising material.

Within this context, SrTiO3 was doped by Nb was mixed with graphene oxide (GO) and conventionally sintered at high temperature in atmosphere of H2/N2 to reduce both Nb-doped SrTiO3 and GO. Addition of reduced GO (rGO) in combination with introduction of Sr vacancies provides a synergistic effect of fastening charge transport and thereby increasing electrical conductivity and suppressing the thermal conductivity. These factors, together with a moderate Seebeck coefficient, result in a high power factor PF ∼1.98 mW/(K2m) and ZT up to 0.29. Such findings offer further prospects for seeking high performance SrTiO3-based TEs by modification with rGO. Deep study of the influence of GO/rGO on other thermoelectric materials is done and present for wide auditory.

  • Open access
  • 24 Reads
Sensory Augmentation Using Subdermal Haptic Feedback

The goal of this study is to introduce an implantable haptic feedback device that allows a user better interaction and feedback from various sensory modules. A thorough analysis of the design of the sensor is provided in this paper. The implantable nature increases the user’s ability to integrate the vibrations into a more natural sense over time. Conscious training associating the vibrations with their meaning and the natural neuroplastic capacity of the brain will allow a user an intuitive and integrated understanding of the linked device. By using a standardized external battery module, design constraints surrounding internal power storage are avoided and present an opportunity for modular sensor packages. Current applications include blood glucose monitoring, radiation dosimetry, and pseudo-echolocation using an array of implants.

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