Low Toxicity Research Articles

High-yield, plant-based production of an antimicrobial peptide with potent activity in a mouse model.

Plants offer a promising chassis for the large-scale, cost-effective production of diverse therapeutics, including antimicrobial peptides (AMPs). However, key advances will reduce production costs, including simplifying the downstream processing and purification steps. Here, using Nicotiana benthamiana plants, we present an improved modular design that enables AMPs to be secreted via the endomembrane system and sequestered in an extracellular compartment, the apoplast. Additionally, we translationally fused an AMP to a mutated small ubiquitin-like modifier sequence, thereby enhancing peptide yield and solubilizing the peptide with minimal aggregation and reduced occurrence of necrotic lesions in the plant. This strategy resulted in substantial peptide accumulation, reaching around 2.9 mg AMP per 20 g fresh weight of leaf tissue. Furthermore, the purified AMP demonstrated low collateral toxicity in primary human skin cells, killed pathogenic bacteria by permeabilizing the membrane and exhibited anti-infective efficacy in a preclinical mouse (Mus musculus) model system, reducing bacterial loads by up to three orders of magnitude. A base-case techno-economic analysis demonstrated the economic advantages and scalability of our plant-based platform. We envision that our work can establish plants as efficient bioreactors for producing preclinical-grade AMPs at a commercial scale, with the potential for clinical applications.

Design, Synthesis, and Evaluation of the Antitubercular Activity of 5-Phenyl Substituted-5, 6-dihydropyrido[2, 3-d]pyrimidine-4, 7(3H, 8H)-dione Compounds.

Tuberculosis (TB) remains a major public health challenge, with research on new anti-TB drugs crucial for global TB elimination efforts. Here, we report a novel class of anti-TB agents. Especially, compounds 5b and 5j exhibited the highest activity [minimum inhibitory concentration (MIC) H37Rv: 0.16 and 0.12 μg/mL]. Chiral resolution was performed on compounds 5b and 5j; the isomers were evaluated for their activity and safety, confirming that the R-isomer 5bb and 5jb displayed significant anti-TB activity (MIC H37Rv: 0.03-0.06 μg/mL; MDR-Mtb: 0.125-0.06 μg/mL) and low hERG toxicity. Further evaluations on 5bb and 5jb demonstrated good metabolic stability, favorable kinetic parameters and oral bioavailability (F: 56.7 and 63.8%, respectively). The results of in vivo activity assessment indicate that 5bb and 5jb exhibit protective and therapeutic effects on zebrafish larvae and adult zebrafish infected with Mycobacterium marinum. Based on these results, compounds 5bb and 5jb are considered promising candidates for further in-depth studies.

Life Cycle of LiFePO4 Batteries: Production, Recycling, and Market Trends.

Significant attention has focused on olivine-structured LiFePO4 (LFP) as a promising cathode active material (CAM) for lithium-ion batteries. This iron-based compound offers advantages over commonly used Co and Ni due to its lower toxicity abundance, and cost-effectiveness. Despite its current commercial use in energy storage technology, there remains a need for cost-effective production methods to create electrochemically active LiFePO4. Consequently, there is ongoing interest in developing innovative approaches for LiFePO4 production. While LFP batteries exhibit significant thermal stability, cycling performance, and environmental benefits, their growing adoption has increased battery disposal rates. Improper disposal practices for waste LFP batteries result in environmental degradation and the depletion of valuable resources. This review comprehensively examines diverse synthesis approaches for generating LFP powders, encompassing conventional methodologies alongside novel procedures. Furthermore, it conducts an in-depth assessment of the methodologies employed in recycling waste LFP batteries. Moreover, it emphasizes the importance of LFP cathode recycling and investigates pretreatment techniques to enhance understanding. Additionally, it provides valuable insights into the recycling process of used LFP batteries, aiming to raise awareness regarding the market for retired LFP batteries and advocate for the enduring sustainability of lithium-ion batteries.

Discovery of Covalent MLKL PROTAC Degraders via Optimization of a Theophylline Derivative Ligand for Treating Necroptosis.

Mixed lineage kinase domain-like pseudokinase (MLKL) initiates necroptosis and could serve as a therapeutic target related to a series of human diseases. Proteolysis-targeting chimeras (PROTACs) are useful tools for degrading pathological proteins and blocking disease processes. Using computer-aided modeling and molecular dynamics simulations, we developed a series of covalent MLKL PROTACs by linking and optimizing a theophylline derivative that covalently targets MLKL. Via structure-activity relationship studies, MP-11 was identified as a potent MLKL PROTAC degrader. Furthermore, MP-11 showed lower toxicity than the original MLKL ligand, exhibiting nanomolar-scale antinecroptotic activity on human cell lines. Xenograft model studies showed that MP-11 effectively degraded MLKL in vivo. Importantly, our study demonstrates that the covalent binding strategy is an effective approach for designing MLKL-targeting PROTACs, serving as a model for developing PROTACs to treat future necroptosis-related human diseases.

Excitonic properties and solar harvesting performance of Cs2ZnY2X2 as quasi-2D mixed-halide perovskites

Due to their low toxicity and high-temperature stability, lead-free quasi-2D metal halide perovskites (MHPs) are promising materials for optoelectronic applications. However, understanding their structural and optoelectronic properties, especially excitonic effects (electron-hole pair, e-h), is challenging due to their quantum well topology. We propose an efficient protocol for band gap correction of Cs2ZnX (X = Cl4, Br2Cl2, and I2Cl2) and Cs2PbI2Cl2 (used as a benchmark) quasi-2D MHPs. This protocol is based on a relativistic quasiparticle approach (DFT-1/2) using density functional theory (DFT). We first examined the hybrid contributions of the halide alloys, leading to excitonic characterization using the Bethe–Salpeter equation within the maximally localized Wannier functions tight-binding method. This method provides a cost-effective approach for describing e-h quasiparticle effects. Additionally, we analyzed the crystal structure, thermodynamic stability, and optoelectronic properties of the newly synthesized Zn-based systems, focusing on their structural stability mechanisms. We found a correlation between the allocation of Cs+ cations in the crystal structure and the formation of two distinct stabilization patterns, influenced by the radii of the metal (Zn or Pb) and halide components. The relativistic correction of the band gap energies yielded results within 10 % of the experimental values. Furthermore, incorporating e-h quasiparticle effects for Cs2PbI2Cl2 resulted in an exciton binding energy of 0.160 eV, in excellent agreement with experimental data. This work represents a significant advance in the optoelectronic characterization of Cs2ZnX systems, previously unexplored for their excitonic properties.

Fungi from Antarctic marine sediment: characterization and assessment for textile dye decolorization and detoxification.

Cold-adapted microorganisms can produce enzymes with activity at low and mild temperatures, which can be applied to environmental biotechnology. This study aimed to characterize 20 Antarctic fungi to identify their genus (ITS rDNA marker) and growth temperatures and evaluate their ability to decolorize and detoxify the textile dye indigo carmine (IC). An individual screening was performed to assess the decolorization and detoxification of IC by the isolates, as well as in consortia with other fungi. The isolates were affiliated with seven ascomycete genera: Aspergillus (n = 4), Cosmospora (n = 2), Leuconeurospora (n = 2), Penicillium (n = 3), Pseudogymnoascus (n = 6), Thelebolus (n = 2), and Trichoderma (n = 1). The two isolates from the genus Leuconeurospora were characterized as psychrophilic, while the others were psychrotolerant. The Penicillium isolates were able to decolorize between 60 and 82% of IC. The isolates identified as Pseudogymnoascus showed the best detoxification capacity, with results varying from 49 to 74%. The consortium using only Antarctic ascomycetes (C1) showed 45% of decolorization, while the consortia with the addition of basidiomycetes (C1 + Peniophora and C1 + Pholiota) showed 40% and 50%, respectively. The consortia C1 with the addition of the basidiomycetes presented a lower toxicity after the treatments. In addition, a higher fungal biomass was produced in the presence of dye when compared with the experiment without the dye, which can be indicative of dye metabolization. The results highlight the potential of marine-derived Antarctic fungi in the process of textile dye degradation. The findings encourage further studies to elucidate the degradation and detoxification pathways of the dye IC by these fungal isolates.

Flexible zinc-ion hybrid supercapacitor based on Co2+-doped polyaniline/V2O5 electrode

With the rapid advancement of renewable energy sources and portable electronic devices, the demand for high-performance energy storage systems is growing, driving continuous progress in supercapacitor technology. Zinc-ion hybrid supercapacitors (ZIHS), known for their higher safety, cost-effectiveness, and environmental friendliness, have become a hot research topic. Vanadium pentoxide (V2O5) possesses flexible multivalence, low cost, low toxicity, wide voltage window, high capacitance, and high energy density. However, its poor electrical conductivity and low cycling stability hinder its electrochemical performance, thus limiting its application in ZIHS. Here, we propose a novel strategy of incorporating Co2+ ions and conductive polyaniline (PANI) with V2O5 (CoVO-PANI) as cathode materials for ZIHS. The synergistic effect between cobalt ions and polyaniline have led to an expansion of the interlayer spacing in CoVO-PANI, which reduce the binding energy of Zn2+ ion insertion, decrease the diffusion barrier of Zn2+ ion insertion, and enhanced the electronic conductivity of the material for electron transport. In result, the CoVO-PANI@CC//2 M ZnSO4//AC@CC can reach the areal capacitance of 847.3 mF cm−2 at 1 mA cm−2. Following 2000 times at 50 mA cm−2, the CoVO-PANI@CC//2 M ZnSO4//AC@CC maintains a retention rate of 81.37 %, and can achieve a Coulombic efficiency of 100 %. The assembled flexible ZIHS device exhibits excellent flexibility and stability, with an areal capacitance of 775.6 mF cm−2 at 1 mA cm−2. This work demonstrates the tremendous potential of CoVO-PANI@CC as a cathode material for ZIHS.

Unraveling the Hemolytic Toxicity Tapestry of Peptides using Chemical Space Complex Networks.

Peptides have emerged as promising therapeutic agents. However, their potential is hindered by hemotoxicity. Understanding the hemotoxicity of peptides is crucial for developing safe and effective peptide-based therapeutics. Here, we employed chemical space complex networks (CSNs) to unravel the hemotoxicity tapestry of peptides. CSNs are powerful tools for visualizing and analyzing the relationships between peptides based on their physicochemical properties and structural features. We constructed CSNs from the StarPepDB database, encompassing 2004 hemolytic peptides, and explored the impact of seven different (dis)similarity measures on network topology and cluster (communities) distribution. Our findings revealed that each CSN extracts orthogonal information, enhancing the motif discovery and enrichment process. We identified 12 consensus hemolytic motifs, whose amino acid composition unveiled a high abundance of lysine, leucine, and valine residues, while aspartic acid, methionine, histidine, asparagine and glutamine were depleted. Additionally, physicochemical properties were used to characterize clusters/communities of hemolytic peptides. To predict hemolytic activity directly from peptide sequences, we constructed multi-query similarity searching models (MQSSMs), which outperformed cutting-edge machine learning (ML)-based models, demonstrating robust hemotoxicity prediction capabilities. Overall, this novel in silico approach uses complex network science as its central strategy to develop robust model classifiers, to characterize the chemical space and to discover new motifs from hemolytic peptides. This will help to enhance the design/selection of peptides with potential therapeutic activity and low toxicity.

γ-Cyclodextrin-metal organic framework as a carrier for trans-N-p-coumaroyltyramine: A study of drug solubability, stability, and inhibitory activity against α-glucosidase.

γ-Cyclodextrin-based metal-organic frameworks (γ-CD-MOF) were successfully synthesized using the solvent diffusion method and applied as carriers for trans-N-p-coumaroyltyramine (N-p-t-CT, NCT) to study the solubability, stability, sustained release and inhibitory activity against α-glucosidase. The solubilization effect of γ-CD-MOF on N-p-t-CT was performed using impregnation (NCT@CD-MOF-1) and co-crystallization (NCT@CD-MOF-2) methods. X-ray diffraction, scanning electron microscope (SEM), fourier transform infrared spectrometer (FTIR), and N2 adsorption/desorption were used to characterize the MOFs before and after loading NCT. The results showed that NCT@CD-MOF-2 had a better solubability for N-p-t-CT, 145.03μg/mg of drug loading capacity could be achieved, and the solubility of NCT@CD-MOF-2 in water was 366 times higher than free N-p-t-CT. In addition, the stabilities of N-p-t-CT under temperature, UV light and pH conditions were greatly improved after encapsulation in γ-CD-MOF. Furthermore, NCT@CD-MOFs had a sustained release of N-p-t-CT over an extended period in vitro due to the primary encapsulation in pore structures. Notably, γ-CD-MOF loaded with N-p-t-CT showed superior inhibitory activity against α-glucosidase compared to free N-p-t-CT. Cytotoxicity studies demonstrated that NCT@CD-MOF-2 had low toxicity in vitro and perfect biocompatibility with HL-7702 cells, and γ-CD-MOF could reduce the toxicity of free N-p-t-CT at higher concentrations.

Discovery of membrane-targeting amphiphilic honokiol derivatives containing an oxazolethione moiety to combat methicillin-resistant Staphylococcus aureus (MRSA) infections

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major pathogen causing infections in hospitals and the community, and there is an urgent need for the development of novel antibacterials to combat MRSA infections. Herein, a series of amphiphilic honokiol derivatives containing an oxazolethione moiety were prepared and evaluated for their in vitro antibacterial and hemolytic activities. The screened optimal derivative, I3, exhibited potent in vitro antibacterial activity against S. aureus and clinical MRSA isolates with MIC values of 2–4 μg/mL, which was superior to vancomycin in terms of its rapid bactericidal properties and was less susceptible to the development of resistance. The SARs analysis indicated that amphiphilic honokiol derivatives with fluorine substituents had better antibacterial activity than those with chlorine and bromine substituents. In vitro and in vivo toxicity studies revealed that I3 has relatively low toxicity. In a MRSA-infected mouse skin abscess model, I3 (5 mg/kg) effectively killed MRSA at the infected site and attenuated the inflammation effects, comparable to vancomycin. In a MRSA-infected mouse sepsis model, I3 (12 mg/kg) was found to significantly reduce the bacterial load in infected mice and increase survival of infected mice. Mechanistic studies indicated that I3 has membrane targeting properties and can interact with phosphatidylglycerol (PG) and cardiolipin (CL) of MRSA cell membranes, thereby disrupting MRSA cell membranes, further inducing the increase of reactive oxygen species (ROS), protein and DNA leakage to achieve rapid bactericidal effects. Finally, we hope that I3 is a potential candidate molecule for the development of antibiotics to conquer superbacteria-related infections.

Enhance hydrogen storage in lightweight solid-state systems based on Poly(vinylnaphthalene)

This article highlights the potential of poly(2-vinylnaphthalene) (PVN) as a novel light-weight solid-state hydrogen storage system for various applications. With an impressive theoretical gravimetric hydrogen capacity of 5.2 wt.-%, PVN stands out for its attractiveness as a hydrogen carrier. The material possesses advantageous characteristics, including moldability, low toxicity, and ease of storage, making it a promising candidate for both stationary and mobile hydrogen storage applications. Experimental findings demonstrate that PVN can be hydrogenated by up to 76 % utilizing an Ru/Al2O3 catalyst at 250 °C for 24 h. Confirmation of the hydrogenation reaction, which results in poly(2-vinyldecalin), was achieved through characterization techniques such as FTIR, 1H NMR, and spectroscopic ellipsometry. The study of the effects of hydrogen pressure and reaction time identified moderate conditions as favorable, though a further exploration of different catalysts is suggested for optimal conversion. A palladium-based catalyst was employed to release hydrogen from the hydrogenated polymer, demonstrating almost complete reversibility of the hydrogenation of poly(2-vinylnaphthalene) with a dehydrogenation yield of 90 %.

Piezoelectric supercapacitors: current trends and future outlook

Abstract The present review analyses the research and development of piezoelectric supercapacitor (PSC)-based self-charging storage devices (SCSDs) over the last few years, with a bird’s-eye view of the prevailing trends and the outlook for the future. Piezoelectric materials, known for their ability to convert mechanical energy into electrical energy, have emerged as a key player in the development of next-generation supercapacitors with self-charging capability. The present review begins with elucidating the fundamental principles of piezoelectricity and piezoelectric generators vis-à-vis materials and properties as well as their integration into supercapacitor design. Advancements in fabrication techniques and the diversity of materials used have been discussed in detail with a focus on various characterization techniques. The review also addresses existing limitations, such as low energy transfer efficiency and material toxicity, as well as presenting strategies to overcome these hurdles and proposing avenues for future research and development.

Characterization of fuel-induced water contamination: chemical composition, odor threshold, and ecotoxicological implications

Fuel spills pose significant environmental risks, particularly to drinking water sources and aquatic ecosystems. The composition of fuels has changed over the decades to reduce fossil greenhouse gas emissions. In Sweden, although the number of spill incidents has declined, with around 600 cases reported annually, there remains limited knowledge on the environmental and health impacts of modern fuels. This study aimed to address this gap through comprehensive chemical analysis and ecotoxicological assessments of 31 fuel samples, including petrol, diesel, fuel oil, and marine gas oil. Using gas chromatography-mass spectrometry (GC-MS), we determined 53 substances, including aromatic and aliphatic hydrocarbons, ethers, esters, and 17 polycyclic aromatic hydrocarbons (PAHs). A key focus was on forming a stable water-accommodated fraction (WAF) to isolate non-dissolved fuel elements from water, which is crucial for assessing subsurface aquatic life and drinking water production impacts. Results indicated significant differences in fuel odor profiles, with ethers enhancing odor intensity. Petrol components showed higher water solubility than diesel, partly due to ethanol. Ecotoxicological tests revealed varying toxicity across fuels, with petrol showing the highest toxicity to aquatic organisms, although activated sludge exhibited resilience. Fuels containing water-soluble ethers posed the highest risks to drinking water, while modern diesel was of lower concern due to its low solubility and toxicity. In freshwater ecosystems, petrol and hydrophobic toxins in fuel oil had severe effects during spills. Overall, this study offers critical insights into the environmental impact of common fuels, supporting improved risk assessment and management strategies for spill mitigation and water resource protection.

Effect of ammonium polyphosphate on flame retardancy of bio-based rigid polyurethane foams

Rigid polyurethane foam (RPUF) has attracted a lot of attention as a multifunctional material. However, the use of fossil fuels in various fields is limited due to their flammability and excessive consumption in the preparation process. In order to solve this problem, a sustainable bio-based RPUF was prepared by ammonium polyphosphate (APP) and lignin-based polyol flame-retardant modification. The impact of APP on the smoke characteristics, flame retardancy, and thermal behavior of lignin-based polyol RPUFs was examined. The modified RPUF (RPUF-20) with 20 wt.% APP had the greatest starting temperature and residual rate. The maximum activation energy (E) and best thermal stability were found in the pyrolysis kinetics calculation utilizing the thermogravimetric trajectory compared with other specimens. Cone showed that when RPUF-20 was compared with RPUF-0, the peak heat release rate was lowered by 79.43%, 72.79%, and 67.91%, and the total heat release was reduced by 50.59%, 56.29%, and 37.14%, respectively. In addition, RPUF-20 had the lowest smoke density, according to the statistics. The current results showed that RPUF-20 had low smoke toxicity and outstanding flame retardancy, which gave rise to a novel notion for RPUFs following flame-retardant modification using biomass.

Bottle-brush polyurethane as water-based lubricant additive for hydrophobic interfaces

Water-based lubricants were limited on chemically inert and hydrophobic interfaces due to the difficulty in forming an effective boundary lubrication layer. In this study, a bottle-brush polyurethane (BBP) lubricant additive was designed to address the issue through the establishment of multiple non-covalent interactions. 1H NMR, FTIR and molecular dynamics (MD) simulation revealed that the backbone and side chains of BBP provided multiple hydrogen bond interactions. QCM-D verified that BBP was capable of constructing a denser interfacial adsorption layer than linear macromolecules. The as-prepared BBP lubricant exhibited outstanding lubrication performance across various hydrophobic interfaces and was better than oleophilic, hydrophilic and amphiphilic lubricants. Meanwhile, BBP lubricant presented extremely low toxicity to cells and earthworms, indicating potential in medical and industrial fields.

N-formylmethionine-leucyl-phenylalanine protects against irradiation-induced damage to hematopoiesis and intestines

BackgroundIonizing radiation (IR), including radiotherapy, can exert lasting harm on living organisms. While liposaccharide (LPS) offers resistance to radiation damage, it also induces toxic responses. Thankfully, an LPS analogue called N-formylmethionine-leucyl-phenylalanine (fMLP) holds the potential to mitigate this toxicity, offering hope for radiation protection.MethodsSurvival of C57BL/6 mice exposed to IR after administration with fMLP/LPS/WR-2721 or saline was recorded. Cell viability and apoptosis assay of bone marrow (BMC), spleen and small intestinal epithelial (HIECs) cells were tested by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Tissue damage was evaluated by Hematoxilin and Eosin (H&E), Ki-67, and TUNEL staining. RNA sequencing was performed to reveal potential mechanisms of fMLP-mediated radiation protection. Flow cytometry and western blot were performed to verify the radiation protection mechanism of fMLP on the cell cycle.ResultsThe survival rates of C57BL/6 mice exposed to ionizing radiation after administering fMLP increased. fMLP demonstrated low toxicity in vitro and in vivo, maintaining cell viability and mitigating radiation-induced apoptosis. Moreover, it protected against tissue damage in the hematopoietic and intestinal system. RNA sequencing shed light on fMLP’s potential mechanism, suggesting its role in modulating innate immunity and cell cycling. This was evidenced by its ability to reverse radiation-induced G2/M phase arrests in HIECs.ConclusionfMLP serves as a promising radioprotective agent, preserving cells and radiosensitive tissues from IR. Through its influence on the cell cycle, particularly reversing radiation-induced arrest in G2/M phases, fMLP offers protection against IR’s detrimental effects.

Anticipating Viral Challenges: A Perspective on Phytochemicals Against Existing and Emerging Viruses

Abstract: Viral infections impact millions of individuals annually and in 2018, the WHO called for global preparedness to address potential high-mortality pathogens, referred to as "Pathogen X," which can include fungi, viruses, parasites, or prions. The constant evolution of RNA viruses leads to continually changing variants, challenging the effectiveness of vac-cines and drugs. In underserved healthcare regions, plant-based phytochemicals offer prom-ise in combating viral diseases due to their ready availability, proven effectiveness, and low toxicity. Amidst the evolving virus variants and recurring fatal outbreaks, especially in re-source-constrained regions, phytochemicals hold promise as potential anti-infective agents. This review delves into plant-based antivirals, aiming to update plant-derived antiviral com-pounds' status against existing and emerging viruses from 2019 to 2023. The study aimed to identify active components from medicinal plants with IC50 and EC50 values against human-infecting viruses. It utilized in vitro and in vivo methods to predict phytochemical mechanisms and enhance bioavailability. Among the phytochemicals studied as antivirals, Emodin, Quercetin, Myricetin, Resveratrol, and Silymarin demonstrated efficacy against multiple viruses. Notably, certain plant compounds were effective against multiple viruses and could serve as potential antiviral treatments. Overall, the review illustrates that harness-ing plant-derived compounds shows promise in combating current and evolving infectious threats.

Design, Synthesis, Molecular Docking, and in vitro Cytotoxicity Studies of Marine Natural Product Herdmanine Derivatives as Multitarget Inhibitor for EGFR and HER2 Breast Cancer Proteins

AbstractBreast cancer is a potentially deadly disease that affects millions of individuals worldwide. Therefore, it is crucial to design highly targeted therapeutic techniques with low toxicity. In this work, we synthesized natural product Herdmanine's ester derivatives and tested them against EGFR and HER2 proteins as multitargated inhibitor of breast cancer progression. Further, the newly synthesized compounds were evaluated for cytotoxicity against breast cancer cell lines MCF‐7, MDA‐MB‐231 and MDA‐MB‐157 and the biocompatibility towards NIH 3T3 cells. Higher toxicity and positive viability profiles of Herdmanine derivatives indicate their potential use for further exploration in breast cancer application.

Development and characterization of a cyclodextrin-based delivery system for enhanced pharmacokinetic and safety profile of oseltamivir

AbstractOseltamivir (OST) phosphate is a prodrug, metabolized by hepatic carboxylesterase to its active metabolite (oseltamivir carboxylate). OST is efficient in treatment of influenza, in both children and adults. The protein bonding of the prodrug and its active metabolite is low (42% and 3%, respectively). It has a short half-life 1–3 h but its active metabolite has a half-life of 6–10 h, permitting twice daily administration. The most common side effect is gastrointestinal disturbances that are usually nausea and vomiting and can be reduced when taken simultaneously with food. OST phosphate is a white powder with bitter taste and the marketed oral suspension uses sorbitol for masking it. Cross-linked cyclodextrin polymers are known for their ability to increase the dissolution rate, solubility, stability, and permeability of insoluble drugs and provide prolonged release. Therefore, they are promising drug delivery systems that could improve its pharmacokinetic properties and patient adherence. In this study we focused on developing a therapeutic system of OST using cyclodextrin polymer crosslinked with pyromellitic dianhydride (PMDA CD) to enhance its pharmacokinetic properties and to improve its compliance. PMDA CD polymer and PMDA CD polymer complex with OST were prepared. Physicochemical characterization by FTIR spectra, thermal analysis, DLS, SEM and EDX confirmed the existence of interaction between the two components. The prepared complex has a different pharmaceutical profile compared to OST, with higher stability and a controlled dissolution profile. Toxicity studies showed that the polymer complex has lower toxicity than OST, suggesting the protective effect of the polymer.

Deep eutectic solvent strategy for green extraction of chlorogenic acid from sea buckthorn: optimization and sustainability

BackgroundSea buckthorn (Hippophae rhamnoides), a deciduous species plant, is widely distributed around the globe, and native to the cold-temperate regions of Europe and Asia. This medicinal herb contains several bioactive constituents including chlorogenic acid. The conventional methods used for the extraction of phenolic antioxidants from natural herbs often result in low yields, high toxicity, and pose environmental hazards limiting their effectiveness and scalability. Therefore, green extraction techniques using deep eutectic solvents, composed of natural, non-toxic, and biodegradable components were applied for extraction of chlorogenic acid from sea buckthorn weed. Fourteen deep eutectic solvent mixtures were prepared and evaluated for extraction yield of chlorogenic acid. Parameters such as hydrogen bond donor-to-hydrogen bond acceptor ratio, liquid-to-solid ratio, shaking speed, and shaking time were optimized for the best mixture.ResultsThe combination of lactic acid and maltose (1:1) was found to give best extraction yield using response surface methodology. The deep eutectic solvent system under optimum conditions produced 12.2 g/100 g of crude extract sea buckthorn containing 174.7 mg gallic acid equivalents (mg GA)/g) of extract. Moreover, the optimized extract exhibited appreciable radical scavenging capacity (91%), trolox equivalent antioxidant capacity (11.2% of extract), and inhibition of peroxide in linoleic acid (80.6%). High-performance liquid chromatography-based characterization revealed the extracts contained chlorogenic acid (20.1 mg/g of extract) as the major constituent.ConclusionsIn summary, the adoption of DES for the extraction of bioactive phenolic constituents from sea buckthorn offers multiple benefits, including economic efficiency, enhanced extraction performance, and environmental sustainability. The findings of this study not only advance the understanding of DES in phytochemical extraction but also pave the way for broader application of green solvents in the natural products industry. Future research should focus on further optimizing DES formulations and scaling up the extraction process to fully realize the potential of this innovative extraction method in commercial applications.