Effect of the Drying Method and Storage Conditions on the Quality and Content of Selected Bioactive Compounds of Green Legume Vegetables.

This study aimed to determine the effect of the drying method (freeze-drying, air-drying), storage period (12 months), and storage conditions (2-4 °C, 18-22 °C) applied to two legume species: green beans and green peas. The raw and dried materials were determined for selected physical parameters typical of dried vegetables, contents of bioactive components (vitamin C and E, total chlorophyll, total carotenoids, ß-carotene, and total polyphenols), antioxidative activity against the DPPH radical, and sensory attributes (overall quality and profiles of color, texture, and palatability). Green beans had a significantly higher content of bioactive components compared to peas. Freeze-drying and cold storage conditions facilitated better retention of these compounds, i.e., by 9-39% and 3-11%, respectively. After 12 months of storage, higher retention of bioactive components, except for total chlorophyll, was determined in peas regardless of the drying method, i.e., by 38-75% in the freeze-dried product and 30-77% in the air-dried product, compared to the raw material.

Induced Self-Assembly of Vitamin E-Spermine/siRNA Nanocomplexes via Spermine/Helix Groove-Specific Interaction for Efficient siRNA Delivery and Antitumor Therapy.

Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self-assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E-spermine/siRNA complexes can further self-assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self-assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE-Su-Sper/DSPE-PEG2000/siSurvivin self-assembled nanocomplexes can accumulate in cancer cells and gradually release siRNA in tumor tissues and show significant antitumor effect in vivo. The self-assembled delivery system provides a novel strategy for highly efficient siRNA delivery.

Effect of talc and vitamin E TPGS on manufacturability, stability and release properties of trilaurin-based formulations for hot-melt coating.

This study was focused on one particular case of hot-melt coating with trilaurin - a solid medium-chain monoacid triglyceride. The challenge of using trilaurin as coating agent in melting-based processes is linked to its relatively low melting profile: 15.6 °C (Tm,α), 35.1 °C ( [Formula: see text] ) and 45.7 °C (Tm,ß). From a process perspective, the only possibility to generate products coated with formulations composed of trilaurin is by setting thermal operational conditions above Tm,α. From a material perspective, this processing possibility depends principally on trilaurin crystallisation which was investigated via a set of analytical techniques including turbidimetry, calorimetry, hot-melt goniometry, and polarised light microscopy. A highly soluble drug model substrate (sodium chloride crystals) was coated with three selected trilaurin-based formulations: (i) trilaurin, (ii) trilaurin plus talc, and (iii) trilaurin plus vitamin E TPGS and talc. Coated salt crystals were then analysed to investigate processing performance, coating quality, stability and release properties under digestion effect. The results show that firstly, talc addition promotes nucleation and crystal growth and, as a consequence, it facilitates the manufacture of trilaurin-based formulations. Secondly, the formulation of a solid triglyceride and a hydrophilic surfactant could potentially cause release instability, but formula (iii) was found to be stabilised by a mechanism whereby trilaurin crystallization enhanced in the presence of talc immobilised vitamin E TPGS in its crystal lattice. Thirdly, talc addition did not significantly influence trilaurin digestion which endows products with an immediate release in lipolytic conditions instead of an extended liberation in pure water. Nor did the addition of one or two additives alter the extent of trilaurin digestion under the conditions studied. These important findings relate to product manufacturability, stability, and release properties. A good understanding of material properties (e.g. crystallisation, polymorphism, digestibility) is essential for melt-processing, lipid coating stabilising and modulation of release profile of solid lipid-coated product, as demonstrated in this case study with trilaurin.

Enhancing Ezetimibe Anticancer Activity Through Development of Drug Nano-Micelles Formulations: A Promising Strategy Supported by Molecular Docking.

Background: Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations. Materials and Methods: Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed. Results: The prepared formulations were in the nano-size range (34.01 ± 2.00-278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC50 against MCF-7 (4.51 µg/mL) and T47D (8.22 µg/mL) cancer cells. When T47D cells were treated with IC50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death. Conclusion: These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer.

Fabrication of D-α-tocopheryl polyethylene glycol 1000 succinates and human serum albumin conjugated chitosan nanoparticles of bosutinib for colon targeting application; in vitro-in vivo investigation.

For more effective chemotherapy and targeted treatment of colorectal cancer, this study seeks to develop chitosan (CH)-human serum albumin (HAS)-D-α-tocopheryl polyethylene glycol 1000 (TPGS) nanoparticles (BOS-CH-HSA-TPGS-NPs) coated with Bosutinib (BOS). Nuclear magnetic resonance (NMR) indicated that chitosan's structure was modified by carbodiimide coupling with HSA. We used a Box-Behnken design to find the ideal region for particle size, zeta potential, and entrapment efficiency, eventually emerging at a formulation with these values: 187.14 ± 3.2 nm, 76.2 ± 0.96 %, and 21.1 ± 2.3 mV. Differential scanning calorimetry (DSC), Transmission electron microscopy (TEM), X-ray diffraction (XRD), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), High-performance liquid chromatography (HPLC) were all used to characterize the sample in detail. At a phosphate buffer pH of 7.4, in vitro drug release tests showed both Higuchi model release (0.954) and Fickian diffusion (n = 0.5). Compared to free BOS, HCT116 cell lines showed considerably higher cytotoxicity in in vitro cytotoxicity assays. In male albino Wistar rats, the BOS-CH-HSA-TPGS-NPs also showed enhanced pharmacokinetics, targeting efficiency, and biocompatibility. When used to the treatment of colorectal cancer, the BOS-CH-HSA-TPGS NPs show promise as a sustained-release therapy with improved therapeutic effects by addressing the challenges of poor solubility, poor permeability, and toxic side effects.

Nanoarchitectonics of doxycycline-loaded vitamin E-D-α-tocopheryl polyethylene glycol 1000 succinate micelles for ovarian cancer stem cell treatment.

Aim: This study aim to develop doxycycline within the D-α-tocopheryl polyethylene glycol 1000 succinate micelle platform as an anticancer stem cell agent. Materials & methods: The optimized nanomicelle formulation was prepared using the solvent casting method and evaluated through physicochemical and biological characterization. Results: Nanomicelles exhibited mean particle sizes of 14.48 nm (polydispersity index: 0.22) using dynamic light scattering and 18.22 nm using transmission electron micrography. Drug loading and encapsulation efficiency were 2% and 66.73%, respectively. Doxycycline-loaded micelles exhibited sustained release, with 98.5% released in 24 h. IC50 values were 20 µg/ml for free drug and 5 µg/ml for micelles after 48 h of cell exposure. A significant 74% reduction in CD44 biomarker and 100% colony formation inhibition were observed. Conclusion: Doxycycline in hemo/biocompatible nanomicelles holds potential for ovarian cancer stem cell therapy.

Cancer, a global leading cause of death, has a significant impact on human health. Among the various types of cancer, ovarian cancer ranks as the seventh most prevalent, posing a significant threat to women and contributing significantly to deaths in this population. Recent studies have highlighted the importance of targeting cancer stem cells to enhance the effectiveness of cancer treatments and prevent tumor relapse. Cancer stem cells are cells that can differentiate into different cell types in a tumor, driving the growth and spread of cancer. Over the past few decades, certain antibiotics, including doxycycline, have emerged as potent and selective anticancer stem cell agents by specifically targeting mitochondrial biogenesis. In line with this, the authors developed a doxycycline-loaded micelle delivery system. Micelles are spheres made of a single layer of a type of fat called phospholipids; they have been combined with drugs to increase the successful delivery and effectiveness of that drug. This research revealed that this micelle formulation demonstrated a fourfold increase in efficacy against ovarian cancer stem cells compared with free antibiotics. Moreover, it efficiently reduced colony formation and CD44 biomarker levels among the stem cells, indicating damage to cancer stem cells. These findings underscore the potential of this doxycycline-loaded micelle system as a promising approach for eradicating ovarian cancer stem cells and improving therapeutic outcomes.

Cellular and Non-cellular Antioxidant Properties of Vitamin E-Loaded Metallic-Quercetin/Polycaprolactone Nanoparticles for the Treatment of Melanogenesis.

Inhibition of melanogenesis by quercetin and vitamin E is extensively reported in the literature, independently, with limitations in antioxidant potential owing to less permeation, solubility, decreased bioavailability, and reduced stability. Thus, the aim of the present study was to synthesize a novel complex of metal ions (copper and zinc) with quercetin to enhance antioxidant properties which were confirmed by docking studies. Polycaprolactone-based nanoparticles of the synthesized complex (PCL-NPs, Q-PCL-NPs, Zn-Q-PCL-NPs, Cu-Q-PCL-NPs) were made later loaded with vitamin E which made the study more interesting in enhancing antioxidant profile. Nanoparticles were characterized for zeta size, charge, and polydispersity index, while physiochemical analysis of nanoparticles was strengthened by FTIR. Cu-Q-PCL-NPs-E showed maximum in vitro release of vitamin E, i.e., 80 ± 0.54%. Non-cellular antioxidant effect by 2,2-diphenyl-1-picrylhydrazyl was observed at 93 ± 0.23% in Cu-Q-PCL-NPs-E which was twofold as compared to Zn-Q-PCL-NPs-E. Michigan Cancer Foundation-7 (MCF-7) cancer cell lines were used to investigate the anticancer and cellular antioxidant profile of loaded and unloaded nanoparticles. Results revealed reactive oxygen species activity of 90 ± 0.32% with the addition of 89 ± 0.64% of its anticancer behavior shown by Cu-Q-PCL-NPs-E after 6 and 24h. Similarly, 80 ± 0.53% inhibition of melanocyte cells and 95 ± 0.54% increase of keratinocyte cells were also shown by Cu-Q-PCL-NPs-E that confirmed the tyrosinase enzyme inhibitory effect. Conclusively, the use of zinc and copper complex in unloaded and vitamin E-loaded nanoparticles can provide enhanced antioxidant properties with inhibition of melanin, which can be used for treating diseases of melanogenesis.

Experimental design of D-α-tocopherol polyethylene glycol 1000 succinate stabilized bile salt based Nano-vesicles for improved cytotoxicity and bioavailability of colchicine binding site inhibitor Candidates: In Vitro, in silico, and pharmacokinetic studies.

Nowadays, conventional anticancer therapy suffers many pitfalls, including drastic side effects and limited therapeutic efficacy resulting from diminished oral bioavailability. So, in an attempt to enhance their poor solubility and oral bioavailability along with the cytotoxic activity, the developed lead compounds (C1 and C2) were loaded in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified vesicles adopting thin film hydration technique. The formulations of the aforementioned candidates (F1 and F2, respectively) were elected as the optimum formula with desirability values of 0.701 and 0.618, respectively. Furthermore, an outstanding enhancement in the drug's cytotoxic activity against different cancer cell lines (MCF-7, HepG-2, MDA-MB-321, A375, and MGC-803) after being included in the nano-TPGS-modified optimum formula was noticed relative to the unformulated compounds. The formula F1 showed the best cytotoxic activities against HepG-2 with an IC50 = 3 µM. Furthermore, regarding MCF-7, F1 was shown to be the most potent and protective among all the tested formulations with an IC50 = 6 µM. Besides, F1 exerted the best caspase 3/7 activity stimulation (around a 5-folds increase) compared to control in the MCF-7 cell line. Notably, it was disclosedthat both C1 and C2 induced cell cycle arrest at the resting S growth phase. Moreover, C1 and C2 decreased tubulin concentrations by approximately 2-folds and 6-folds, respectively. Meanwhile, the conducted molecular docking studies ensure the eligible binding affinities of the assessed compounds. Besides, MD simulations were performed for 1000 ns to confirm the docking results and study the exact behavior of the target candidates (C1 and C2) toward the CBS.

Activity and Characterization of Tocopherol Oxidase in Corn Germs and Its Relationship with Oil Color Reversion.

Color reversion has long been a major problem for the vegetable oil industry, and the enzymatic oxidation of γ-tocopherol is thought to trigger this phenomenon. In this study, first, the extraction, purification, and detailed characterization of tocopherol oxidase from fresh corn germs were performed. Then, the relationship between the enzyme reaction of γ-tocopherol and oil color reversion was verified. The results showed that the membrane-free extracts of raw corn germ performed specific catalysis of tocopherol in the presence of lecithin. In terms of the oxidation product, tocored (the precursor of color reversion) was detected in the mixture after the catalytic reactions, indicating that this anticipated enzyme reaction was probably correlated with the color reversion. Furthermore, the optimal pH and temperature for the tocopherol oxidase enzyme were 4.6 and 20 °C, respectively. In addition, ascorbic acid at 1.0 mM completely inhibited the enzymatic reaction.

Dual role of polyglycerol vitamin E succinate in emulsions: An efficient antioxidant emulsifier.

α-Tocopherol, as an oil-soluble vitamin with strong antioxidant activity. It is the most naturally abundant and biologically active form of vitamin E in humans. In this study, a novel emulsifier (PG20-VES) was synthesized by attaching hydrophilic twenty-polyglycerol (PG20) to hydrophobic vitamin E succinate (VES). This emulsifier was shown to have a relatively low critical micelle concentration (CMC = 3.2 µg/mL). The antioxidant activities and emulsification properties of PG20-VES were compared with those of a widely used commercial emulsifier: D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS). PG20-VES exhibited a lower interfacial tension, stronger emulsifying capacity and similar antioxidant property to TPGS. An in vitro digestion study showed that lipid droplets coated by PG20-VES were digested under simulated small intestine conditions. This study showed that PG20-VES is an efficient antioxidant emulsifier, which may have applications in the formulation of bioactive delivery systems in the food, supplement, and pharmaceutical industries.

Isolation of plastochromanol-8 from flaxseed oil by countercurrent separation methods.

The naturally occurring antioxidant plastochromanol-8 (PC-8) is a member of the tocochromanol (vitamin E) family which features eight unsaturated isoprene units in the side chain compared to three in the case of γ-tocotrienol. Due to the lack of a commercially available PC-8 standard, we developed a route to gain relevant amounts of highly pure PC-8. Specifically, ∼320 g flaxseed oil was saponified and the bulky PC-8 was enriched by gel permeation chromatography. It followed countercurrent chromatography using the solvent system n-hexane/benzotrifluoride/acetonitrile (20:7:13, v/v/v). The final purification was achieved by centrifugal partition chromatography using the novel solvent system hexamethyldisiloxane/acetonitrile (1:1, v/v). This step provided ∼26 mg PC-8 (>99.5 %, according to HPLC, GC and NMR analysis). Two further, hitherto unknown minor tocochromanols (<1 % of PC-8) were detected and could be identified to be plastochromanol-7 (PC-7) and plastochromanol-9 (PC-9), i.e. tocochromanols with seven and nine unsaturated isoprene units, respectively, in the side chain.

External Factors Modulating Vaping-Induced Thermal Degradation of Vitamin E Acetate.

Despite previous studies indicating the thermal stability of vitamin E acetate (VEA) at low temperatures, VEA has been shown to readily decompose into various degradation products such as alkenes, long-chain alcohols, and carbonyls such as duroquinone (DQ) at vaping temperatures of <200 °C. While most models simulate the thermal decomposition of e-liquids under pyrolysis conditions, numerous factors, including vaping behavior, device construction, and the surrounding environment, may impact the thermal degradation process. In this study, we investigated the role of the presence of molecular oxygen (O2) and transition metals in promoting thermal oxidation of e-liquids, resulting in greater degradation than predicted by pure pyrolysis. Thermal degradation of VEA was performed in inert (N2) and oxidizing atmospheres (clean air) in the absence and presence of Ni-Cr and Cu-Ni alloy nanopowders, metals commonly found in the heating coil and body of e-cigarettes. VEA degradation was analyzed using thermogravimetric analysis (TGA) and gas chromatography/mass spectrometry (GC/MS). While the presence of O2 was found to significantly enhance the degradation of VEA at both high (356 °C) and low (176 °C) temperatures, the addition of Cu-Ni to oxidizing atmospheres was found to greatly enhance VEA degradation, resulting in the formation of numerous degradation products previously identified in VEA vaping emissions. O2 and Cu-Ni nanopowder together were also found to significantly increase the production of OH radicals, which has implications for e-liquid degradation pathways as well as the potential risk of oxidative damage to biological systems in real-world vaping scenarios. Ultimately, the results presented in this study highlight the importance of oxidation pathways in VEA thermal degradation and may aid in the prediction of thermal degradation products from e-liquids.

Vaping Aerosols from Vitamin E Acetate and Tetrahydrocannabinol Oil: Chemistry and Composition.

The popularity of vaping cannabis products has increased sharply in recent years. In 2019, a sudden onset of electronic cigarette/vaping-associated lung injury (EVALI) was reported, leading to thousands of cases of lung illness and dozens of deaths due to the vaping of tetrahydrocannabinol (THC)-containing e-liquids that were obtained on the black market. A potential cause of EVALI has been hypothesized due to the illicit use of vitamin E acetate (VEA) in cannabis vape cartridges. However, the chemistry that modifies VEA and THC oil, to potentially produce toxic byproducts, is not well understood under different scenarios of use. In this work, we quantified carbonyls, organic acids, cannabinoids, and terpenes in the vaping aerosol of pure VEA, purified THC oil, and an equal volume mixture of VEA and THC oil at various coil temperatures (100-300 °C). It was found under the conditions of our study that degradation of VEA and cannabinoids, including Δ9-THC and cannabigerol (CBG), occurred via radical oxidation and direct thermal decomposition pathways. Evidence of terpene degradation was also observed. The bond cleavage of aliphatic side chains in both VEA and cannabinoids formed a variety of smaller carbonyls. Oxidation at the ring positions of cannabinoids formed various functionalized products. We show that THC oil has a stronger tendency to aerosolize and degrade compared to VEA at a given temperature. The addition of VEA to the e-liquid nonlinearly suppressed the formation of vape aerosol compared to THC oil. At the same time, toxic carbonyls including formaldehyde, 4-methylpentanal, glyoxal, or diacetyl and its isomers were highly enhanced in VEA e-liquid when normalized to particle mass.

Formation of Redox-Active Duroquinone from Vaping of Vitamin E Acetate Contributes to Oxidative Lung Injury.

In late 2019, the outbreak of e-cigarette or vaping-associated lung injuries (EVALIs) in the United States demonstrated to the public the potential health risks of vaping. While studies since the outbreak have identified vitamin E acetate (VEA), a diluent of tetrahydrocannabinol (THC) in vape cartridges, as a potential contributor to lung injuries, the molecular mechanisms through which VEA may cause damage are still unclear. Recent studies have found that the thermal degradation of e-liquids during vaping can result in the formation of products that are more toxic than the parent compounds. In this study, we assessed the role of duroquinone (DQ) in VEA vaping emissions that may act as a mechanism through which VEA vaping causes lung damage. VEA vaping emissions were collected and analyzed for their potential to generate reactive oxygen species (ROS) and induce oxidative stress-associated gene expression in human bronchial epithelial cells (BEAS-2B). Significant ROS generation by VEA vaping emissions was observed in both acellular and cellular systems. Furthermore, exposure to vaping emissions resulted in significant upregulation of NQO1 and HMOX-1 genes in BEAS-2B cells, indicating a strong potential for vaped VEA to cause oxidative damage and acute lung injury; the effects are more profound than exposure to equivalent concentrations of DQ alone. Our findings suggest that there may be synergistic interactions between thermal decomposition products of VEA, highlighting the multifaceted nature of vaping toxicity.

Thermal Degradants Identified from the Vaping of Vitamin E Acetate.

Studies have suggested that vitamin E acetate (VEA), when used in an electronic vaping device, undergoes thermal degradation and is considered one of the main contributors in e-cigarette or vaping product use-associated lung injury (EVALI). Using a Borgwaldt 5.1 linear smoker, a SVS250 Electronic Vaporizer and two types of tank systems, VEA was analyzed for degradation products produced via the Cooperation Centre for Scientific Research Relative to Tobacco method 81 when the filter containing vaporized VEA was extracted using acetonitrile. Two of the major products identified were 2,3,5,6-tetramethyl-1,4-benzoquinone and 2,6,10,14-tetramethyl-1-pentadecene, which were confirmed using analytical standards and gas chromatography-high-resolution mass spectrometry (GC-HRMS). Additional synthesis of 4-acetoxy-2,3,5,6-tetramethyl-2,4-cyclohexadienone and subsequent characterization using nuclear magnetic resonance and GC-HRMS suggested that this is not one of the products produced. Identification of these degradants will allow future studies to quantify and examine the degradants in vivo and in vitro as biomarkers for exposure and toxicity assessment.

Design, synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer's disease.

A novel series of chalcone-Vitamin E-donepezil hybrids was designed and developed based on multitarget-directed ligands (MTDLs) strategy for treating Alzheimer's disease (AD). The biological results revealed that compound 17f showed good AChE inhibitory potency (ratAChE IC50 = 0.41 µM; eeAChE IC50 = 1.88 µM). Both the kinetic analysis and docking study revealed that 17f was a mixed type AChE inhibitor. 17f was also a good antioxidant (ORAC = 3.3 eq), selective metal chelator and huMAO-B inhibitor (IC50 = 8.8 µM). Moreover, it showed remarkable inhibition of self- and Cu2+-induced Aß1-42 aggregation with a 78.0 and 93.5% percentage rate at 25 µM, respectively, and disassembled self-induced and Cu2+-induced aggregation of the accumulated Aß1-42 fibrils with 72.3 and 84.5% disaggregation rate, respectively. More importantly, 17f exhibited a good neuroprotective effect on H2O2-induced PC12 cell injury and presented good blood-brain barrier permeability in vitro. Thus, 17f was a promising multi-target-directed ligand for treating AD.

Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.

Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology.

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.

A multifunctional nano-delivery system enhances the chemo-co-phototherapy of tumor multidrug resistance via mitochondrial-targeting and inhibiting P-glycoprotein-mediated efflux.

Despite the excellent progress of chemotherapy and phototherapy in tumor treatment, their effectiveness on multidrug-resistant (MDR) tumors is still unsatisfactory. One of the main obstacles is drug efflux caused by P-glycoprotein in MDR cells. Herein, we developed a nano-delivery system that combines a P-glycoprotein inhibitor with chemotherapy and phototherapy to overcome MDR. Briefly, the system is prepared by the self-assembly of a ROS-triggered doxorubicin prodrug (PTD) and mitochondrial-targeted D-α-tocopherol polyethyleneglycol succinate (TPP-TPGS), in which a photoactive drug, IR780, is encapsulated (PTD/TT/IR780). PTD/TT/IR780 can target the release of TPP-TPGS, doxorubicin and IR780 at the mitochondrial site of MDR cells through ROS trigger. D-α-Tocopherol polyethyleneglycol succinate (TPGS) is a P-glycoprotein inhibitor, which will reduce the efflux of doxorubicin and IR780 from MDR cells. Under irradiation of an 808 nm near-infrared laser, IR780 generates heat and ROS, causing mitochondrial damage and prompting MDR cell apoptosis. At the same time, ROS can reduce the ATP content, which inhibits the P-glycoprotein function. In addition, an increase in the ROS generates positive feedback, allowing more nanoparticles to be cleaved and further promoting payload release in MDR cells, thereby enhancing the synergistic efficacy of chemotherapy and phototherapy. The in vitro cellular assay showed that PTD/TT/IR780 significantly inhibited MDR cell proliferation at a very low drug concentration (IC50 = 0.27 µg mL-1 doxorubicin-equivalent concentration). In vivo animal experiments based on BALB/c nude mice bearing MCF-7/ADR tumors confirmed a superior antitumor efficacy and an excellent biosafety profile. These findings demonstrate that this multifunctional nanoplatform provides a new approach for the treatment of MDR tumors.

N-trimethyl chitosan coated nano-complexes enhance the oral bioavailability and chemotherapeutic effects of gemcitabine.

N-trimethyl chitosan (TMC) is a multifunctional polymer that can be used in various nanoparticle forms in the pharmaceutical, nutraceutical and biomedical fields. In this study, TMC was used as a mucoadhesive adjuvant to enhance the oral bioavailability and hence antitumour effects of gemcitabine formulated into nanocomplexes composed of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) conjugated with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). A central composite design was applied to achieve the optimal formulation. Cellular uptake and drug transportation studies revealed the nanocomplexes permeate over the intestinal cells via adsorptive-mediated and caveolae-mediated endocytosis. Pharmacokinetic studies demonstrated the oral drug bioavailability of the nanocomplexes was increased 5.1-fold compared with drug solution. In pharmacodynamic studies, the formulation reduced tumour size 3.1-fold compared with the drug solution. The data demonstrates that TMC modified nanocomplexes can enhance gemcitabine oral bioavailability and promote the anticancer efficacy.