bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome-Wide Analysis of Human Liver Reveals Age-Related Differences in the Expression of Select Functional Gene Clusters and Evidence for a PPP1R10-Governed ‘Aging Cascade’
Authors: Schreiter Thomas , Gieseler Robert K. , Vílchez-Vargas Ramiro , Jauregui Ruy , Sowa Jan-Peter , Klein-Scory Susanne , Broering Ruth , Croner Roland S. , Treckmann Jürgen W. , Link Alexander , Canbay Ali
Published: December 2021

A transcriptome-wide analysis of human liver for demonstrating differences between young and old humans has not yet been performed. However, identifying major age-related alterations in hepatic gene expression may pinpoint ontogenetic shifts with important hepatic and systemic consequences, provide novel pharmacogenetic information, offer clues to efficiently counteract symptoms of old age, and improve the overarching understanding of individual decline. Next-generation sequencing (NGS) data analyzed by the Mann–Whitney nonparametric test and Ensemble Feature Selection (EFS) bioinformatics identified 44 transcripts among 60,617 total and 19,986 protein-encoding transcripts that significantly (p = 0.0003 to 0.0464) and strikingly (EFS score > 0.3:16 transcripts; EFS score > 0.2:28 transcripts) differ between young and old livers. Most of these age-related transcripts were assigned to the categories ‘regulome’, ‘inflammaging’, ‘regeneration’, and ‘pharmacogenes’. NGS results were confirmed by quantitative real-time polymerase chain reaction. Our results have important implications for the areas of ontogeny/aging and the age-dependent increase in major liver diseases. Finally, we present a broadly substantiated and testable hypothesis on a genetically governed ‘aging cascade’, wherein PPP1R10 acts as a putative ontogenetic master regulator, prominently flanked by IGFALS and DUSP1. This transcriptome-wide analysis of human liver offers potential clues towards developing safer and improved therapeutic interventions against major liver diseases and increased insights into key mechanisms underlying aging.
Recent Advances in Photodynamic Therapy against Fungal Keratitis
Authors: Hung Jia-Horung , Lee Chaw-Ning , Hsu Huai-Wen , Ng I-Son , Wu Chi-Jung , Yu Chun-Keung , Lee Nan-Yao , Chang Yun , Wong Tak-Wah
Published: December 2021

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.
Current and Emerging Strategies for Enhancing Antibody Delivery to the Brain
Authors: Bajracharya Rinie , Caruso Alayna C. , Vella Laura J. , Nisbet Rebecca M.
Published: December 2021

For the treatment of neurological diseases, achieving sufficient exposure to the brain parenchyma is a critical determinant of drug efficacy. The blood–brain barrier (BBB) functions to tightly control the passage of substances between the bloodstream and the central nervous system, and as such poses a major obstacle that must be overcome for therapeutics to enter the brain. Monoclonal antibodies have emerged as one of the best-selling treatment modalities available in the pharmaceutical market owing to their high target specificity. However, it has been estimated that only 0.1% of peripherally administered antibodies can cross the BBB, contributing to the low success rate of immunotherapy seen in clinical trials for the treatment of neurological diseases. The development of new strategies for antibody delivery across the BBB is thereby crucial to improve immunotherapeutic efficacy. Here, we discuss the current strategies that have been employed to enhance antibody delivery across the BBB. These include (i) focused ultrasound in combination with microbubbles, (ii) engineered bi-specific antibodies, and (iii) nanoparticles. Furthermore, we discuss emerging strategies such as extracellular vesicles with BBB-crossing properties and vectored antibody genes capable of being encapsulated within a BBB delivery vehicle.
Transdermal Drug Delivery in the Pig Skin
Authors: Ordiz Ignacio , Vega José A. , Martín-Sanz Raquel , García-Suárez Olivia , del Valle Miguel E. , Feito Jorge
Published: December 2021

Transdermal delivery can be accomplished through various mechanisms including formulation optimization, epidermal stratum corneum barrier disruption, or directly by removing the stratum corneum layer. Microneedling, electroporation, a combination of both and also the intradermal injection known as mesotherapy have proved efficacy in epidermal-barrier disruption. Here we analyzed the effects of these methods of epidermal-barrier disruption in the structure of the skin and the absorption of four compounds with different characteristics and properties (ketoprofen, biotin, caffein, and procaine). Swine skin (Pietrain x Durox) was used as a human analogue, both having similar structure and pharmacological release. They were biopsied at different intervals, up to 2 weeks after application. High-pressure liquid chromatography and brightfield microscopy were performed, conducting a biometric analysis and measuring histological structure and vascular status. The performed experiments led to different results in the function of the studied molecules: ketoprofen and biotin had the best concentrations with intradermal injections, while delivery methods for obtaining procaine and caffein maximum concentrations changed on the basis of the lapsed time. The studied techniques did not produce significant histological alterations after their application, except for an observed increase in Langerhans cells and melanocytes after applying electroporation, and an epidermal thinning after using microneedles, with variable results regarding dermal thickness. Although all the studied barrier disruptors can accomplish transdermal delivery, the best disruptor is dependent on the particular molecule.
Evaluation of the Immune Response of a Candidate Phage-Based Vaccine against Rhipicephalus microplus (Cattle Tick)
Authors: González-Mora Alejandro , Calvillo-Rodríguez Kenny Misael , Hernández-Pérez Jesús , Rito-Palomares Marco , Martínez-Torres Ana Carolina , Benavides Jorge
Published: December 2021

Cattle tick (Rhipicephalus microplus) represents a severe problem causing substantial economic losses, estimated in billions of dollars annually. Currently, chemical acaricides represent the most widely used control method. However, several problems such as resistance have been described. Phage-based vaccines represent a fast and low-cost tool for antigen delivery. In this regard, the objective of the present work was to develop a candidate phage-based vaccine displaying a cattle tick antigen (Bm86-derived Sbm7462 antigen) on the surface of bacteriophage M13. Phage ELISA and dot blotting analysis confirmed the display of the antigen. Vaccine immunogenicity was evaluated using a bovine monocyte-derived dendritic cell-based ex vivo assay and a murine in vivo assay. The ex vivo model showed the maturation of dendritic cells after being pulsed with the phage-based vaccine. The humoral response was confirmed in the in vivo assay. These results demonstrated the capacity of the phage-based vaccine to induce both humoral and cellular immune-specific responses. Importantly, this is the first report describing a control method for cattle ticks using a candidate phage-based vaccine. Further studies to evaluate the immunogenicity in a bovine model are needed. The current approach represents a promising alternative to control cattle tick infestations.
Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid–Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration
Authors: Guadarrama-Escobar Omar Rodrigo , Sánchez-Vázquez Ivonne , Serrano-Castañeda Pablo , Chamorro-Cevallos German Alberto , Rodríguez-Cruz Isabel Marlen , Sánchez-Padrón Adalí Yisell , Anguiano-Almazán Ericka , Peña-Juárez Ma. Concepción , Méndez-Albores Abraham , Domínguez-Delgado Clara Luisa , Mercado-Márquez Crisóforo , Rodríguez-Pérez Betsabé , Escobar-Chávez José Juan
Published: December 2021

The methacrylic acid–ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/− 9.14 nm with a PDI of 0.37085 +/− 0.014 and a zeta potential of −13.7125 +/− 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.
Silica Coating of Ferromagnetic Iron Oxide Magnetic Nanoparticles Significantly Enhances Their Hyperthermia Performances for Efficiently Inducing Cancer Cells Death In Vitro
Authors: Iacoviță Cristian , Fizeșan Ionel , Nitica Stefan , Florea Adrian , Barbu-Tudoran Lucian , Dudric Roxana , Pop Anca , Vedeanu Nicoleta , Crisan Ovidiu , Tetean Romulus , Loghin Felicia , Lucaciu Constantin Mihai
Published: December 2021

Increasing the biocompatibility, cellular uptake, and magnetic heating performance of ferromagnetic iron-oxide magnetic nanoparticles (F-MNPs) is clearly required to efficiently induce apoptosis of cancer cells by magnetic hyperthermia (MH). Thus, F-MNPs were coated with silica layers of different thicknesses via a reverse microemulsion method, and their morphological, structural, and magnetic properties were evaluated by multiple techniques. The presence of a SiO2 layer significantly increased the colloidal stability of F-MNPs, which also enhanced their heating performance in water with almost 1000 W/gFe as compared to bare F-MNPs. The silica-coated F-MNPs exhibited biocompatibility of up to 250 μg/cm2 as assessed by Alamar Blues and Neutral Red assays on two cancer cell lines and one normal cell line. The cancer cells were found to internalize a higher quantity of silica-coated F-MNPs, in large endosomes, dispersed in the cytoplasm or inside lysosomes, and hence were more sensitive to in vitro MH treatment compared to the normal ones. Cellular death of more than 50% of the malignant cells was reached starting at a dose of 31.25 μg/cm2 and an amplitude of alternating magnetic field of 30 kA/m at 355 kHz.
Nanoantibiotics Based in Mesoporous Silica Nanoparticles: New Formulations for Bacterial Infection Treatment
Authors: Álvarez Elena , González Blanca , Lozano Daniel , Doadrio Antonio L. , Colilla Montserrat , Izquierdo-Barba Isabel
Published: December 2021

This review focuses on the design of mesoporous silica nanoparticles for infection treatment. Written within a general context of contributions in the field, this manuscript highlights the major scientific achievements accomplished by professor Vallet-Regí’s research group in the field of silica-based mesoporous materials for drug delivery. The aim is to bring out her pivotal role on the envisage of a new era of nanoantibiotics by using a deep knowledge on mesoporous materials as drug delivery systems and by applying cutting-edge technologies to design and engineer advanced nanoweapons to fight infection. This review has been divided in two main sections: the first part overviews the influence of the textural and chemical properties of silica-based mesoporous materials on the loading and release of antibiotic molecules, depending on the host–guest interactions. Furthermore, this section also remarks on the potential of molecular modelling in the design and comprehension of the performance of these release systems. The second part describes the more recent advances in the use of mesoporous silica nanoparticles as versatile nanoplatforms for the development of novel targeted and stimuli-responsive antimicrobial nanoformulations for future application in personalized infection therapies.
Silver Nanoparticles as Potential Antiviral Agents
Authors: Ratan Zubair Ahmed , Mashrur Fazla Rabbi , Chhoan Anisha Parsub , Shahriar Sadi Md. , Haidere Mohammad Faisal , Runa Nusrat Jahan , Kim Sunggyu , Kweon Dae-Hyuk , Hosseinzadeh Hassan , Cho Jae Youl
Published: December 2021

Since the early 1990s, nanotechnology has led to new horizons in nanomedicine, which encompasses all spheres of science including chemistry, material science, biology, and biotechnology. Emerging viral infections are creating severe hazards to public health worldwide, recently, COVID-19 has caused mass human casualties with significant economic impacts. Interestingly, silver nanoparticles (AgNPs) exhibited the potential to destroy viruses, bacteria, and fungi using various methods. However, developing safe and effective antiviral drugs is challenging, as viruses use host cells for replication. Designing drugs that do not harm host cells while targeting viruses is complicated. In recent years, the impact of AgNPs on viruses has been evaluated. Here, we discuss the potential role of silver nanoparticles as antiviral agents. In this review, we focus on the properties of AgNPs such as their characterization methods, antiviral activity, mechanisms, applications, and toxicity.
Clinical Relevance of Novel Polymorphisms in the Dihydropyrimidine Dehydrogenase (DPYD) Gene in Patients with Severe Fluoropyrimidine Toxicity: A Spanish Case-Control Study
Authors: Soria-Chacartegui Paula , Villapalos-García Gonzalo , López-Fernández Luis A. , Navares-Gómez Marcos , Mejía-Abril Gina , Abad-Santos Francisco , Zubiaur Pablo
Published: December 2021

Among cancer patients treated with fluoropyrimidines, 10–40% develop severe toxicity. Polymorphism of the dihydropyrimidine dehydrogenase (DPYD) gene may reduce DPD function, the main enzyme responsible for the metabolism of fluoropyrimidines. This leads to drug accumulation and to an increased risk of toxicity. Routine genotyping of this gene, which usually includes DPYD *HapB3, *2A, *13 and c.2846A > T (D949V) variants, helps predict approximately 20–30% of toxicity cases. For DPD intermediate (IM) or poor (PM) metabolizers, a dose adjustment or drug switch is warranted to avoid toxicity, respectively. Societies such as the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF), the Dutch Pharmacogenetics Working Group (DPWG) or the Clinical Pharmacogenetics Implementation Consortium (CPIC) and regulatory agencies (e.g., the Spanish Medicines Agency, AEMPS) already recommend DPYD routine genotyping. However, the predictive capacity of genotyping is currently still limited. This can be explained by the presence of unknown polymorphisms affecting the function of the enzyme. In this case-control work, 11 cases of severe fluoropyrimidine toxicity in patients who did not carry any of the four variants mentioned above were matched with 22 controls, who did not develop toxicity and did not carry any variant. The DPYD exome was sequenced (Sanger) in search of potentially pathogenic mutations. DPYD rs367619008 (c.187 A > G, p.Lys63Glu), rs200643089 (c.2324 T > G, p.Leu775Trp) and rs76387818 (c.1084G > A, p.Val362Ile) increased the percentage of explained toxicities to 38–48%. Moreover, there was an intronic variant considered potentially pathogenic: rs944174134 (c.322-63G > A). Further studies are needed to confirm its clinical relevance. The remaining variants were considered non-pathogenic.
Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys
Authors: Eikrem Oystein , Kotopoulis Spiros , Popa Mihaela , Mayoral Safont Mireia , Fossan Kjell Ove , Leh Sabine , Landolt Lea , Babickova Janka , Gudbrandsen Oddrun Anita , Gilja Odd Helge , Riedel Bettina , Schjøtt Jan , McCormack Emmet , Marti Hans-Peter
Published: December 2021

The use of ultrasound and microbubble-enhanced drug delivery, commonly referred to as sonoporation, has reached numerous clinical trials and has shown favourable results. Nevertheless, the microbubbles and acoustic path also pass through healthy tissues. To date, the majority of studies have focused on the impact to diseased tissues and rarely evaluated the impact on healthy and collateral tissue. The aim of this study was to test the effect and feasibility of low-intensity sonoporation on healthy kidneys in a mouse model. In our work here, we used a clinical diagnostic ultrasound system (GE Vivid E9) with a C1-5 ultrasound transducer combined with a software modification for 20-µs-long pulses to induce the ultrasound-guided drug delivery of doxorubicin (DOX) in mice kidneys in combination with SonoVue® and Sonazoid™ microbubbles. The acoustic output settings were within the commonly used diagnostic ranges. Sonoporation with SonoVue® resulted in a significant decrease in weight vs. DOX alone (p = 0.0004) in the first nine days, whilst all other comparisons were not significant. Ultrasound alone resulted in a 381% increase in DOX uptake vs. DOX alone (p = 0.0004), whilst SonoVue® (p = 0.0001) and Sonazoid™ (p < 0.0001) further increased the uptake nine days after treatment (419% and 493%, respectively). No long-standing damage was observed in the kidneys via histology. In future sonoporation and drug uptake studies, we therefore suggest including an “ultrasound alone” group to verify the actual contribution of the individual components of the procedure on the drug uptake and to perform collateral damage studies to ensure there is no negative impact of low-intensity sonoporation on healthy tissues.
Biphasic Drug Release from Rolled-Up Gelatin Capsules with a Cylindrical Cavity
Authors: Mzoughi Jihane , Vandamme Thierry , Luchnikov Valeriy
Published: December 2021

Biphasic drug delivery systems are used for quick release of a specific amount of drug for immediate amelioration of a patient’s state, followed by sustained release, to avoid repeated administration. This type of delivery is often necessary for pain management and the treatment of many pathologies, such as migraines, hypertension, and insomnia. In this work, we propose a novel architecture of a biphasic release media that does not need the rapidly disintegrating layer and that allows for easily setting the sustained release rate. A drug-containing capsule is made by rolling up a thermally crosslinked gelatin strip on which drug reservoirs are formed by casting. The quick-release reservoir (QRR) is placed at the strip’s extremity, from which the rolling starts, while the sustained-release reservoir (SRR) is formed in the middle part of the strip. The strip is rolled around a cylinder that is a few millimeters wide, which is removed after rolling. The roll is stabilized by transglutaminase-catalyzed crosslinking of the consecutive shells. A biphasic release is successfully demonstrated with the use of model fluorescent drugs for single-dye and double-dye systems in phosphate-buffered saline (PBS) solution with pH = 7.4. In vitro, the drug from the QRR, placed at the walls of the cavity of the roll, is released immediately upon the capsule’s contact with the PBS solution. The drug from the SRR, embedded between the roll’s layers, diffuses steadily, with the lag time defined by the radial position of the reservoir.
Application of Lipid-Based Nanocarriers for Antitubercular Drug Delivery: A Review
Authors: Buya Aristote B. , Witika Bwalya A. , Bapolisi Alain M. , Mwila Chiluba , Mukubwa Grady K. , Memvanga Patrick B. , Makoni Pedzisai A. , Nkanga Christian I.
Published: December 2021

The antimicrobial drugs currently used for the management of tuberculosis (TB) exhibit poor bioavailability that necessitates prolonged treatment regimens and high dosing frequency to achieve optimal therapeutic outcomes. In addition, these agents cause severe adverse effects, as well as having detrimental interactions with other drugs used in the treatment of comorbid conditions such as HIV/AIDS. The challenges associated with the current TB regimens contribute to low levels of patient adherence and, consequently, the development of multidrug-resistant TB strains. This has led to the urgent need to develop newer drug delivery systems to improve the treatment of TB. Targeted drug delivery systems provide higher drug concentrations at the infection site, thus leading to reduced incidences of adverse effects. Lipid-based nanocarriers have proven to be effective in improving the solubility and bioavailability of antimicrobials whilst decreasing the incidence of adverse effects through targeted delivery. The potential application of lipid-based carriers such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, nano and microemulsions, and self-emulsifying drug delivery systems for the treatment of TB is reviewed herein. The composition of the investigated lipid-based carriers, their characteristics, and their influence on bioavailability, toxicity, and sustained drug delivery are also discussed. Overall, lipid-based systems have shown great promise in anti-TB drug delivery applications. The summary of the reviewed data encourages future efforts to boost the translational development of lipid-based nanocarriers to improve TB therapy.
The Feasibility of Pressurised Intraperitoneal Aerosolised Virotherapy (PIPAV) to Administer Oncolytic Adenoviruses
Authors: Tate Sophia J. , Van de Sande Leen , Ceelen Wim P. , Torkington Jared , Parker Alan L.
Published: December 2021

Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially enhancing treatment efficacy. Here, we assess the feasibility of pressurised intraperitoneal aerosolised virotherapy (PIPAV) to deliver a different class of anticancer agents, oncolytic adenoviruses, in vitro and in vivo. Methods: Adenoviral vectors expressing reporter genes green fluorescence protein (Ad5.GFP) or firefly luciferase (Ad5.Luc) were subject to pressurised aerosolisation. The ability of the virus to survive PIPAV was assessed in vitro and in vivo by monitoring reporter gene activity. Wistar rats subjected to PIPAV were assessed for any adverse procedure related events. Results: In vitro transduction assays demonstrated that Ad5 retained viability following pressurised aerosolisation and could transduce permissive cells equally effectively as non-aerosolised control vector. PIPAV was well tolerated in rats, although minimal transduction was observed following intraperitoneal administration. Conclusions: PIPAV appears viable and well tolerated, though in vivo efficacy requires further optimisation.
Dually Cross-Linked Core-Shell Structure Nanohydrogel with Redox–Responsive Degradability for Intracellular Delivery
Authors: Deng Siyuan , Gigliobianco Maria , Mijit Emin , Minicucci Marco , Cortese Manuela , Campisi Barbara , Voinovich Dario , Battistelli Michela , Salucci Sara , Gobbi Pietro , Lupidi Giulio , Zambito Giorgia , Mezzanotte Laura , Censi Roberta , Di Martino Piera
Published: December 2021

A redox-responsive nanocarrier is a promising strategy for the intracellular drug release because it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation conditions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electron microscopy, and further confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via the Michael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell structure nanohydrogel can be considered a promising tool for the potential intracellular delivery of different pharmaceutical applications, including for cancer therapy.
Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier
Authors: Lee David , Minko Tamara
Published: December 2021

Treatment of neurodegenerative diseases or other central nervous system (CNS) disorders has always been a significant challenge. The nature of the blood-brain barrier (BBB) limits the penetration of therapeutic molecules to the brain after oral or parenteral administration, which, in combination with hepatic metabolism and drug elimination and inactivation during its journey in the systemic circulation, decreases the efficacy of the treatment, requires high drug doses and often induces adverse side effects. Nose-to-brain drug delivery allows the direct transport of therapeutic molecules by bypassing the BBB and increases drug concentration in the brain. The present review describes mechanisms of nose-to-brain drug delivery and discusses recent advances in this area with especial emphasis on nanotechnology-based approaches.
Experimental and Statistical Analysis of Saw Mill Wood Waste Composite Properties for Practical Applications
Authors: Khan Muhammad Usman , Abas Muhammad , Noor Sahar , Salah Bashir , Saleem Waqas , Khan Razaullah
Published: December 2021

The utilization of composite materials is increasing at a growing rate in almost all types of products, due to their strength-to-stiffness ratio. From this perspective, natural waste composites, i.e., wood waste composites, have also been investigated for their effective and sustainable employment. This paper deals with the application of hard and soft wood waste (i.e., acacia and cedar wood) with epoxy resin polymer to develop high strength and thermally stable wood composites. Mechanical (tensile, flexural, impact, and hardness) and thermal properties of samples are studied using Differential Scanning Calorimeter (DSC) and Thermo Gravimetric Analysis (TGA), respectively. The properties are evaluated by varying the type of wood waste and its percentage by weight. Based on the Taguchi Orthogonal Array Mixture Design, eighteen experiments are investigated. Analysis of variance (ANOVA) results show that wood waste type and wood waste content have a significant effect on all mechanical properties. From the TGA analysis, it is predicted that both types of wood waste composites exhibit similar thermal-induced degradation profiles in terms of the initial and final degradation temperatures. From the DSC results, higher glass transition temperature Tg is detected in 10% of the hardwood waste composite, and a reducing tendency of glass transition temperature Tg is observed with exceeding wood waste content. Moreover, hardwood waste at 10% demonstrated improved decomposition temperature Td, due to strong adhesion between waste and matrix.
Fabrication of Micro-Groove on the Surface of CFRP to Enhance the Connection Strength of Composite Part
Authors: Xu Bin , Wei Meng-Yang , Wu Xiao-Yu , Fu Lian-Yu , Luo Feng , Lei Jian-Guo
Published: December 2021

Carbon fiber-reinforced plastic (CFRP) has the advantages of being light weight, high strength, and corrosion resistant. At present, it is widely used in the lightweight design of automobile parts. The manufacturing of lightweight parts inevitably involves the connection between CFRP and the polymer material. The connection strength between CFRP and the polymer material significantly affects the service life of the composite parts. Taking CFRP and polyamide 6 (PA6) injection-molded composite parts as an example, this paper proposed a technological method to enhance the connection strength between CFRP and PA6. The proposed method was to fabricate micro-groove structures on the CFRP surface by compression molding. These micro-groove structures effectively increased the injection-molding area of the composite parts, thus enhancing the connection strength between CFRP and PA6. This paper presented a detailed study on the compression-molding process of micro-grooves on the CFRP surface, and successfully obtained the appropriate parameters. Finally, PA6 was used for injection molding on the CFRP with micro-grooves at an injection pressure of 8 MPa, an injection temperature of 240 °C, a holding pressure of 5 MPa, and a holding time of 2.5 s. The experimental results show that the micro-groove array structures on the CFRP surface could effectively improve the tensile strength of the connection interface in the composite parts. Compared with the composite part without micro-grooves, the tensile strength of the composite part with micro-grooves was increased by 80.93%. The composite parts prepared in this paper are mainly used in automobile interiors and the research results of this paper meet the actual needs of the enterprise.
Hybrid Composite Material Reinforced with Carbon Nanolaminates for Gradient Stiffness: Preparation and Characterization
Authors: Rodríguez-Ortiz Alvaro , Muriel-Plaza Isabel , Alía-García Cristina , Pinilla-Cea Paz , Suárez-Bermejo Juan C.
Published: December 2021

Currently, the procurement of lightweight, tough, and impact resistant materials is garnering significant industrial interest. New hybrid materials can be developed on the basis of the numerous naturally found materials with gradient properties found in nature. However, previous studies on granular materials demonstrate the possibility of capturing the energy generated by an impact within the material itself, thus deconstructing the initial impulse into a series of weaker impulses, dissipating the energy through various mechanisms, and gradually releasing undissipated energy. This work focuses on two production methods: spin coating for creating a granular material with composition and property gradients (an acrylonitrile–butadiene–styrene (ABS) polymer matrix reinforced by carbon nanolaminates at 0.10%, 0.25%, and 0.50%) and 3D printing for generating viscoelastic layers. The aim of this research was to obtain a hybrid material from which better behaviour against shocks and impacts and increased energy dissipation capacity could be expected when the granular material and viscoelastic layers were combined. Nondestructive tests were employed for the morphological characterization of the nanoreinforcement and testing reinforcement homogeneity within the matrix. Furthermore, the Voronoï tessellation method was used as a mathematical method to supplement the results. Finally, mechanical compression tests were performed to reveal additional mechanical properties of the material that had not been specified by the manufacturer of the 3D printing filaments.
Nanocomposite of Fullerenes and Natural Rubbers: MARTINI Force Field Molecular Dynamics Simulations
Authors: Kitjanon Jiramate , Khuntawee Wasinee , Phongphanphanee Saree , Sutthibutpong Thana , Chattham Nattaporn , Karttunen Mikko , Wong-ekkabut Jirasak
Published: December 2021

The mechanical properties of natural rubber (NR) composites depend on many factors, including the filler loading, filler size, filler dispersion, and filler-rubber interfacial interactions. Thus, NR composites with nano-sized fillers have attracted a great deal of attention for improving properties such as stiffness, chemical resistance, and high wear resistance. Here, a coarse-grained (CG) model based on the MARTINI force field version 2.1 has been developed and deployed for simulations of cis-1,4-polyisoprene (cis-PI). The model shows qualitative and quantitative agreement with the experiments and atomistic simulations. Interestingly, only a 0.5% difference with respect to the experimental result of the glass transition temperature (Tg) of the cis-PI in the melts was observed. In addition, the mechanical and thermodynamical properties of the cis-PI-fullerene(C60) composites were investigated. Coarse-grained molecular dynamics (MD) simulations of cis-PI-C60 composites with varying fullerene concentrations (0–32 parts per hundred of rubber; phr) were performed over 200 microseconds. The structural, mechanical, and thermal properties of the composites were determined. The density, bulk modulus, thermal expansion, heat capacity, and Tg of the NR composites were found to increase with increasing C60 concentration. The presence of C60 resulted in a slight increasing of the end-to-end distance and radius of the gyration of the cis-PI chains. The contribution of C60 and cis-PI interfacial interactions led to an enhancement of the bulk moduli of the composites. This model should be helpful in the investigations and design of effective fillers of NR-C60 composites for improving their properties.
Fabrication and Characterization of Polypyrrole/Multi-Walled Carbon Nanotubes Thin Films Using Thermal Evaporation
Authors: Attar Alaa , Alharthy Rima D. , Zwawi Mohammed , Algarni Mohammed , Albatati Faisal , Bassyouni Mohamed , Abdel-Aziz Mohamed Helmy , Zoromba Mohamed Shafick , Al-Hossainy Ahmed F.
Published: December 2021

Polypyrrole/multiwalled carbon nanotubes composites (PPy/MWCNTs) were produced in an acidic solution utilizing an in situ oxidative polymerization method using ferric chloride as an oxidizing agent and sodium dodecyl sulfate as a soft template. Thermal evaporation was used to fabricate thin films from polypyrrole/multiwalled carbon nanotube composites. The resulting composites were examined by different techniques to explore their morphology, structural and electrical characteristics. The surface morphology analysis revealed that polypyrrole structure is a two-dimensional film with impeded nanoparticles and the thickness of coated PPy around the MWCNTs decreases when increasing the amount of MWCNTs. XRD analysis revealed that the average crystallite size of the prepared composites is 62.26 nm. The direct energy gap for PPy is affected by a factor ranging from 2.41 eV to 1.47 eV depending on the contents of MWCNTs. The thin film’s optical properties were examined using experimental and TDDFT-DFT/DMOl3 simulation techniques. The optical constants and optical conductivity of the composites were calculated and correlated. The structural and optical characteristics of the simulated nanocomposites as single isolated molecules accord well with the experimental results. The nanocomposite thin films demonstrated promising results, making them a viable candidate for polymer solar cell demands. Under optimal circumstances, the constructed planar heterojunction solar cells with a 75 ± 3 nm layer of PPy/MWCNTs had a power conversion efficiency (PCE) of 6.86%.
Enhanced Solar Photocatalytic Reduction of Cr(VI) Using a (ZnO/CuO) Nanocomposite Grafted onto a Polyester Membrane for Wastewater Treatment
Authors: Ashar Ambreen , Bhatti Ijaz Ahmad , Jilani Asim , Mohsin Muhammad , Rasul Sadia , Iqbal Javed , Shakoor Muhammad Bilal , Al-Sehemi Abdullah G. , Wageh S. , Al-Ghamdi Ahmed A.
Published: December 2021

Among chemical water pollutants, Cr(VI) is a highly toxic heavy metal; solar photocatalysis is a cost-effective method to reduce Cr(VI) to innocuous Cr(III). In this research work, an efficient and economically feasible ZnO/CuO nanocomposite was grafted onto the polyester fabric ZnO/CuO/PF through the SILAR method. Characterization by SEM, EDX, XRD, and DRS confirmed the successful grafting of highly crystalline, solar active nanoflakes of ZnO/CuO nanocomposite onto the polyester fabric. The grafting of the ZnO/CuO nanocomposite was confirmed by FTIR analysis of the ZnO/CuO/PF membrane. A solar photocatalytic reduction reaction of Cr(VI) was carried out by ZnO/CuO/PF under natural sunlight (solar flux 5–6 kW h/m2). The response surface methodology was employed to determine the interactive effect of three reaction variables: initial concentration of Cr(VI), pH, and solar irradiation time. According to UV/Vis spectrophotometry, 97% of chromium was removed from wastewater in acidic conditions after four hours of sunlight irradiation. ZnO/CuO/PF demonstrated reusability for 11 batches of wastewater under natural sunlight. Evaluation of Cr(VI) reduction was also executed by complexation of Cr(VI) and Cr(III) with 1, 5-diphenylcarbazide. The total percentage removal of Cr after solar photocatalysis was carried out by AAS of the wastewater sample. The ZnO/CuO/PF enhanced the reduction of Cr(VI) metal from wastewater remarkably.
Photoswitchable Zirconium MOF for Light-Driven Hydrogen Storage
Authors: Butova Vera V. , Burachevskaya Olga A. , Podshibyakin Vitaly A. , Shepelenko Evgenii N. , Tereshchenko Andrei A. , Shapovalova Svetlana O. , Il’in Oleg I. , Bren’ Vladimir A. , Soldatov Alexander V.
Published: December 2021

Here, we report a new photosensitive metal–organic framework (MOF) that was constructed via the modification of UiO-66-NH2 with diarylethene molecules (DAE, 4-(5-Methoxy-1,2-dimethyl-1H-indol-3-yl)-3-(2,5-dimethylthiophen-3-yl)-4-furan-2,5-dione). The material that was obtained was a highly crystalline porous compound. The photoresponse of the modified MOF was observed via UV–Vis and IR spectroscopy. Most of the DAE molecules inside of the UiO-66-pores had an open conformation after synthesis. However, the equilibrium was able to be shifted further toward an open conformation using visible light irradiation with a wavelength of 520 nm. Conversely, UV-light with a wavelength of 450 nm initiated the transformation of the photoresponsive moieties inside of the pores to a closed modification. We have shown that this transformation could be used to stimulate hydrogen adsorption–desorption processes. Specifically, visible light irradiation increased the H2 capacity of modified MOF, while UV-light decreased it. A similar hybrid material with DAE moieties in the UiO-66 scaffold was applied for hydrogen storage for the first time. Additionally, the obtained results are promising for smart H2 storage that is able to be managed via light stimuli.
Alkali Concentration and Diluent Effects on Properties of Grape Cane Fiber-Reinforced Polymer Composites
Authors: Bakar Balkis F. A. , Kamke Frederick A.
Published: December 2021

The main objective of this study was to investigate the properties of polymer composites reinforced with grape cane fibers. The fibers were subjected to a sodium hydroxide (NaOH) treatment at two treatment concentrations to extract the fibers as well as fiber surface treatment. Panels were fabricated by hand lay-up and compression molding according to different fiber types, namely outer bark (OB) and whole (W) fibers. The whole fiber was a mixture of OB and inner bark (IB) fibers. Grape cane fibers were used as the reinforcement material for unsaturated polyester (UPE) resin panels. Acrylated epoxidized soybean oil (AESO) was used as a reactive diluent material with the UPE resin, and the results were compared with panels prepared with commercial styrene–UPE. There were inconsistent alkali treatment concentration effects on the mechanical properties and water absorption. However, panels fabricated with the whole bark fibers that have been treated with 1 wt % NaOH and had AESO–UPE resin resulted in the best tensile and flexural strength.
Polymers as Encapsulating Agents and Delivery Vehicles of Enzymes
Authors: da S. Pereira Adejanildo , Souza Camila P. L. , Moraes Lidiane , Fontes-Sant’Ana Gizele C. , Amaral Priscilla F. F.
Published: December 2021

Enzymes are versatile biomolecules with broad applications. Since they are biological molecules, they can be easily destabilized when placed in adverse environmental conditions, such as variations in temperature, pH, or ionic strength. In this sense, the use of protective structures, as polymeric capsules, has been an excellent approach to maintain the catalytic stability of enzymes during their application. Thus, in this review, we report the use of polymeric materials as enzyme encapsulation agents, recent technological developments related to this subject, and characterization methodologies and possible applications of the formed bioactive structures. Our search detected that the most explored methods for enzyme encapsulation are ionotropic gelation, spray drying, freeze-drying, nanoprecipitation, and electrospinning. α-chymotrypsin, lysozyme, and β-galactosidase were the most used enzymes in encapsulations, with chitosan and sodium alginate being the main polymers. Furthermore, most studies reported high encapsulation efficiency, enzyme activity maintenance, and stability improvement at pH, temperature, and storage. Therefore, the information presented here shows a direction for the development of encapsulation systems capable of stabilizing different enzymes and obtaining better performance during application.
A Customized Knee Antibiotic-Loaded PMMA Spacer: A Preliminary Design Analysis
Authors: Balato Marco , Petrarca Carlo , Quercia Antonio , Riccio Aniello , Sellitto Andrea , Campi Jessica , Borriello Anna , Zarrelli Mauro , Balato Giovanni
Published: December 2021

A preliminary design of customized antibiotic-loaded poly-methyl-methacrylate (ALPMMA) spacer characterized by an appropriate footprint according to the specific patient’s anatomy and a reliable mechanical response to severe functional loads (i.e., level walking and 45° bent knee) is reported. The targeted virtual prototyping process takes origin from a novel patented 3D geometrical conceptualization characterized by added customization features and it is validated by a preliminary FEM-based analysis. Mechanical and thermomechanical properties of the antibiotic-doped orthopedic PMMA cement, which will be used for the future prototype manufacturing, were measured experimentally by testing samples taken during a real day-running orthopedic surgery and manufactured according to the surgeon protocol. FEM analysis results indicate that small area is subjected to intensive stresses, validating the proposed geometry from the mechanical point of view, under the two loading scenarios, moreover the value of safety margins results positive, and this is representative of the lower stress magnitude compared to the critical material limits. The experimental data confirm that the presence of antibiotic will last during the surgeon period moreover, the temperature dependent modulus of the bone cement is slightly affected by the body range temperature whereas it will drastically drop for higher temperature out the range of interest. A complete customization, according to a patient anatomy, and the corresponding real prototype spacer will be manufactured by 3D printing techniques, and it will be validated by destructive testing during the second stage of this activity before commercialization.
Improvement of Polytetrafluoroethylene Membrane High-Efficiency Particulate Air Filter Performance with Melt-Blown Media
Authors: Shim Euijin , Jang Jeong-Phil , Moon Jai-Joung , Kim Yeonsang
Published: December 2021

Polytetrafluoroethylene (PTFE) membrane filters are widely used in low-load application areas, such as industrial cleanrooms, due to their low initial pressure drop. In this study, melt-blown (MB) nonwoven was introduced as a pre-filtration layer at the front end of a high-efficiency particulate air (HEPA) filter to improve the filter performance of the PTFE membrane. Pre-filtration reduces the average particle size, which reaches the PTFE membrane and reduces the dust load on the HEPA filters. A comparative analysis of the HEPA filters by composite MB and PTFE was conducted. Regarding the MB composite on the PTFE, low-weight and high-weight MB composites were effective in increasing dust filtration efficiency, and the dust loading capacity of the PTFE composite with high-weight MB increased by approximately three times that of the PTFE membrane. In addition, the filter was installed on an external air conditioner in an actual use environment and showed a high efficiency of 99.984% without a change in differential pressure after 120 days.