Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-π and π-π interactions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.
Coronavirus disease 2019 (COVID-19) has spread across the world, and no specific antiviral drugs have yet been approved to combat this disease. Favipiravir (FAV) is an antiviral drug that is currently in clinical trials for use against COVID-19. However, the delivery of FAV is challenging because of its limited solubility, and its formulation is difficult with common organic solvents and water. To address these issues, four FAV ionic liquids (FAV-ILs) were synthesized as potent antiviral prodrugs and were fully characterized by nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectrometry, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), derivative thermogravimetry (DTG), and differential scanning calorimetry (DSC). The aqueous solubility and in vivo pharmacokinetic properties of the FAV-ILs were also evaluated. The FAV-ILs exhibited improved aqueous solubility by 78 to 125 orders of magnitude when compared with that of free FAV. Upon oral dosing in mice, the absolute bioavailability of the β-alanine ethyl ester FAV formulation was increased 1.9-fold compared with that of the control FAV formulation. The peak blood concentration, elimination half-life, and mean absorption time of FAV were also increased by 1.5-, 2.0-, and 1.5-fold, respectively, compared with the control. Furthermore, the FAV in the FAV-ILs exhibited significantly different biodistribution compared with the control FAV formulation. Interestingly, drug accumulation in the lungs and liver was improved 1.5-fold and 1.3-fold, respectively, compared with the control FAV formulation. These results indicate that the use of ILs exhibits potential as a simple, scalable strategy to improve the solubility and oral absorption of hydrophobic drugs, such as FAV.
Oral delivery of the sparingly soluble drug methotrexate (MTX) is challenging owing to its poor bioavailability and low solubility. To address this challenge, the present study reports the conversion of MTX into a series of five ionic liquids (ILs) comprising a cationic component-i.e., cholinium (Cho), tetramethylammonium (TMA), tetrabutylphosphonium (TBP), or an amino acid ester-and an anionic component-i.e., MTX. The biocompatibility, pharmacokinetics, tissue distribution, and antitumor efficacy of each MTX-based IL were investigated to determine its usefulness as a pharmaceutical. Oral administration to mice revealed that proline ethyl ester MTX (IL[ProEt][MTX]) had 4.6-fold higher oral bioavailability than MTX sodium, followed by aspartic diethyl ester MTX, IL[TBP][MTX], IL[Cho][MTX], and IL[TMA][MTX]. The peak plasma concentration, elimination half-life, area under the plasma concentration, mean absorption time, and body clearance of IL[ProEt][MTX] were significantly (p
To assess the extent to which people with diabetes in low- and middle-income countries (LMIC) of Asia and the Middle East met evidence-based care recommendations through a systematic review of published literature.
We report a facile synthesis of zinc oxide (ZnO) nanorod arrays using an optimized, chemical bath deposition method on glass, PET and Si substrates. The morphological and structural properties of the ZnO nanorod arrays were investigated using various techniques such as field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) measurements, which revealed the formation of dense ZnO nanorods with a single crystal, hexagonal wurtzite structure. The aspect ratio of the single-crystal ZnO nanorods and the growth rate along the (002) direction was found to be sensitive to the substrate type. The lattice constants and the crystallite size of the fabricated ZnO nanorods were calculated based on the XRD data. The obtained results revealed that the increase in the crystallite size is strongly associated with the growth conditions with a minor dependence on the type of substrate. The Raman spectroscopy measurements confirmed the existence of a compressive stress in the fabricated ZnO nanorods. The obtained results illustrated that the growth of high quality, single-crystal ZnO nanorods can be realized by adjusting the synthesis conditions.
Ionic liquid (IL) surfactants have attracted great interest as promising substitutes for conventional surfactants owing to their exceptional and favorable physico-chemical properties. However, most IL surfactants are not eco-friendly and form unstable micelles, even when using a high concentration of the surfactant. In this study, we prepared a series of halogen-free and biocompatible choline-fatty-acid-based ILs with different chain lengths and degrees of saturation, and we then investigated their micellar properties in aqueous solutions. Characterization of the synthesized surface-active ILs (SAILs) was performed by 1H and 13C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and elemental analysis. The surface-active properties of the SAILs were investigated by tensiometry, conductometry, and dynamic light scattering measurements. The critical micelle concentration of the SAILs was found to be 2-4 times lower than those of conventional surfactants. The thermodynamic properties of micellization (ΔG0m, ΔH0m, and ΔS0m) indicate that the micellization process of the SAILs is spontaneous, stable, and entropy-driven at room temperature. The cytotoxicity of the SAILs was evaluated using mammalian cell line NIH 3T3. Importantly, [Cho][Ole] shows lower toxicity than the analogous ILs with conventional surfactants. These results clearly suggest that these environmentally friendly SAILs can be used as a potential alternative to conventional ILs for various purposes, including biological applications.
This study evaluates the mechanical, durability, and residual compressive strength (after being exposed to 20, 120, 250, 400 and 600 °C) of mortar that uses recycled iron powder (RIP) as a fine aggregate. Within this context, mechanical strength, shrinkage, durability, and residual strength tests were performed on mortar made with seven different percentages (0%, 5%, 10%, 15%, 20%, 30% and 50%) of replacement of natural sand (NS) by RIP. It was found that the mechanical strength of mortar increased when replaced with up to 30% NS by RIP. In addition, the increase was 30% for compressive, 18% for tensile, and 47% for flexural strength at 28 days, respectively, compared to the reference mortar (mortar made with 100% NS). Shrinkage was observed for the mortar made with 100% NS, while both shrinkage and expansion occurred in the mortar made with RIP, especially for RIP higher than 5%. Furthermore, significantly lower porosity and capillary water absorption were observed for mortar made with up to 30% RIP, compared to that made with 100% NS, which decreased by 36% for porosity and 48% for water absorption. As the temperature increased, the strength decreased for all mixes, and the drop was more pronounced for the temperatures above 250 °C and 50% RIP. This study demonstrates that up to 30% RIP can be utilized as a fine aggregate in mortar due to its better mechanical and durability performances.
The fabrication of Nano-based shielding materials is an advancing research area in material sciences and nanotechnology. Although bulky lead-based products remain the primary choice for radiation protection, environmental disadvantages and high toxicity limit their potentials, necessitating less costly, compatible, eco-friendly, and light-weight alternatives. The theme of the presented investigation is to compare the ionization radiation shielding potentialities of the lead acetate (LA), lead nitrate (LN), and bismuth nitrate (BN)-doped zinc oxide nanorods-based thin films (ZONRs-TFs) produced via the chemical bath deposition (CBD) technique. The impact of the selected materials' doping content on morphological and structural properties of ZONRs-TF was investigated. The X-ray diffractometer (XRD) analyses of both undoped and doped TFs revealed the existence of hexagonal quartzite crystal structures. The composition analysis by energy dispersive (EDX) detected the corrected elemental compositions of the deposited films. Field emission scanning electronic microscope (FESEM) images of the TFs showed highly porous and irregular surface morphologies of the randomly aligned NRs with cracks and voids. The undoped and 2 wt.% BN-doped TFs showed the smallest and largest grain size of 10.44 nm and 38.98 nm, respectively. The linear attenuation coefficient (µ) values of all the optimally doped ZONRs-TFs measured against the X-ray photon irradiation disclosed their excrement shielding potency. The measured µ values of the ZONRs-TFs displayed the trend of 1 wt.% LA-doped TF > 1 wt.% LN-doped TF > 3 wt.% BN-doped TF > undoped TFs). The values of μ of the ZONRs-TFs can be customized by adjusting the doping contents, which in turn controls the thickness and morphology of the TFs. In short, the proposed new types of the LA-, LN- and BN-doped ZONRs-TFs may contribute towards the development of the prospective ionization radiation shielding materials.
Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.
Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19.
The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.