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Pancreatic cancer (PC) is one of the most lethal malignancies worldwide and its incidence is increasing. Chemotherapy is often associated to limited efficacy, poor targeting and systemic toxicity. In this work, the hydrophilic gemcitabine (GEM), widely used in PC treatment alone or in combination, was conjugated with vitamin E succinate (VES) and encapsulated in Soluplus® micelles. This prodrug approach facilitated encapsulation of the anticancer drug into the self-assembled copolymer micelles. Soluplus®/VES-GEM micelles were optimized regarding the ratio of the components and the preparation process. The micelles were small-sized (<80 nm), monodisperse, and highly stable, efficiently retaining the conjugate drug and showing significant antiproliferative activity against BxPC3 cell line. To improve biofunctionalization and targeting properties of prepared Soluplus®/VES-GEM micelles, biomimetic modification with PC cell membrane was further attempted by co-extruding PC cell membrane (BxPC3) nanovesicles with Soluplus®/VES-GEM micelles. Several protocols were attempted to prepare the BxPC3-modified Soluplus®/VES-GEM micelles and the outcomes were analyzed in detail. Overall, the results pave the way to innovative PC-targeted nanotherapies by maximizing GEM encapsulation in hydrophobic compartments with high stability and affinity. The results also highlight the need of higher resolution techniques to characterize cell membrane coating of nanocarriers bearing highly hydrophilic shells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Vitamin E ( -tocopherol) and cholesterol are crucial components in cellular protection and physiological processes. Their uses in biological media face challenges due to their poor solubility and stability., Objective: The study investigated the complex interactions of these bioactive compounds in various encapsulation systems of cyclodextrin and liposome, as well as dispersion in PEG-6000, in an attempt to improve the viability, motility, and preservation of ovine sperm cells., Materials and Methods: The work explored the in vitro dissolution kinetics of vitamin E (d-tocopherol) and cholesterol using semi-empirical models., Results: The release profiles of VitE and Chl varied considerably, depending on the specific carrier systems. For liposome-loaded VitE and Chl, the Korsmeyer-Peppas model gave the best fit; for CD/VitE and CD/Chl, the Higuchi model provided the best fit, whereas for PEG-6000 dispersions (VitE and Chl) both the Higuchi and Korsmeyer-Peppas models demonstrated the excellent fit. All systems indicated a Fickian diffusion mechanism dictated by the concentration gradient. The delivery of VitE and Chl with CD, liposome and PEG dispersion significantly increased sperm mobility and motility. The effect on the VCL parameter was the greatest by liposome-loaded VitE and Chl, followed by CD encapsulation and PEG-6000 dispersion., Conclusion: The dynamics of vitamin E and cholesterol within innovative delivery systems offers valuable insights into the development of advanced solutions in reproductive health, particularly on improving the viability, motility of refrigerated ovine sperm cells. Doi.org/10.54680/fr24510110712.

Aceclofenac (ACE) is a drug that was precisely devised to circumvent the shortcomings associated with diclofenac. However, ACE too corresponds to nonsteroidal anti-inflammatory drug (NSAID)-related adverse effects, but with a lower amplitude. The present investigation seeks to develop liposomes loaded with ACE adopting a central composite design (CCD) and formulate a chitosan-based hydrogel for synergistic anti-inflammatory efficacy and improved ACE dermal administration. On the basis of preliminary vesicle size, Poly Dispersity Index (PDI), and drug entrapment, the composition of lipid, cholesterol, and vitamin E TPGS were chosen as independent variables. The formulation composition met the specifications for an optimum liposomal formulation, with total lipid concentration (13.5% w/w), cholesterol concentration (10% w/w), and surfactant concentration (2% w/w). With particle size and PDI of 174.22 ± 5.46 nm and 0.285 ± 0.01 respectively, the optimised formulation achieved an entrapment effectiveness of 92.08 ± 3.56%. Based on the CCD design, the optimised formulation Acec-Lipo opt was chosen and was subsequently transformed to a chitosan-based gel formulation for in vitro drug release, penetration through the skin, in vivo analgesic therapeutic activity, and skin irritation testing. % age oedema inhibition was found to be greatest with the Acec-Lipo opt gel formulation, followed by Acec gel. These results reinforce the notion that the inclusion of chitosan resulted in a synergistic effect despite the same strength of the drug. The findings suggested that Acec-Lipo incorporated in chitosan gel for skin targeting might be an effective formulation for topical ACE administration in clinical subjects., (© 2024. Controlled Release Society.)

Background: Chemotherapeutic drugs have some drawbacks in antineoplastic therapy, mainly containing seriously toxic side effects caused by injection and multi-drug resistance (MDR). Co-delivery with two or more drugs via nanomicelles is a promising strategy to solve these problems. Oral chemotherapy is increasingly preferred owing to its potential to enhance the life quality of patients., Methods and Results: The study intended to develop mixed micelles using D-α-Tocopherol poly(ethylene glycol) 1000 succinate (TPGS) and soluplus for the co-encapsulation of docetaxel (DTX) and curcumin (CUR), marked as (DTX+CUR)-loaded mixed micelles, treating drug-resistant breast cancer by oral administration. The (DTX+CUR)-loaded mixed micelles had a uniform particle size (~64 nm), high drug loading and encapsulation efficiency, in vitro sustained-release properties and good pH-dependent stability. In vitro cell study, the (DTX+CUR)-loaded mixed micelles displayed the highest cellular uptake, cytotoxicity, cell apoptosis-inducing rates and cell ROS-inducing levels on MCF-7/Adr cells. Notably, in vivo pharmacokinetic studies, (DTX+CUR)-loaded mixed micelles enhanced markedly the oral absorption of DTX compared to pure DTX, with a relative oral bioavailability of 574%. The (DTX+CUR)-loaded mixed micelles by oral administration had the same anticancer efficacy as taxotere by injection in resistant breast cancer bearing mice., Conclusion: (DTX+CUR)-loaded mixed micelles could provide a potential formulation for treating drug-resistant breast cancers by oral administration., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Dian et al.)

It has generally been accepted that vitamin E refers to a group of tocochromanols, α-, β-, γ-, and δ-tocopherols and the corresponding four tocotrienols. Recently, Azzi and colleagues proposed to restrict the term vitamin E only to RRR-α-tocopherol, not to other tocopherols and tocotrienols (Azzi A et al. Free Radic Biol Med. 2023; 207:178-180. doi: 10.1016/j.freeradbiomed.2023.06.029). The aim of this paper is to express our opinion on the nomenclature of vitamin E based on available scientific data. In our opinion, it would be inappropriate to exclude all the tocochromanols other than RRR-α-tocopherol from the vitamin E group at this stage when the molecular mechanisms showing how vitamin E deficiency causes diseases such as ataxia and how vitamin E prevents/reverses such diseases are not elucidated. Understanding of whole functions of tocochromanols including underlying mechanisms and dynamics is essential before revision of currently accepted definition of vitamin E. The potential roles of γ-tocopherol and tocotrienols are discussed despite whether they are vitamin function should be clarified in the future studies., Competing Interests: Declaration of competing interest There is no declaration of competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The outbreak of e-cigarette or vaping use-associated lung injury (EVALI) in the United States in 2019 led to a total of 2807 hospitalizations with 68 deaths. While the exact causes of this vaping-related lung illness are still being debated, laboratory analyses of products from victims of EVALI have shown that vitamin E acetate (VEA), an additive in some tetrahydrocannabinol (THC)-containing products, is strongly linked to the EVALI outbreak. Because of its similar appearance and viscosity to pure THC oil, VEA was used as a diluent agent in cannabis oils in illicit markets. A potential mechanism for EVALI may involve VEA's thermal decomposition product, ketene, a highly poisonous gas, being generated under vaping conditions. In this study, a novel approach was developed to evaluate ketene production from VEA vaping under measurable temperature conditions in real-world devices. Ketene in generated aerosols was captured by two different chemical agents and analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method takes advantage of the high sensitivity and specificity of tandem mass spectrometry and appears to be more suitable than GC-MS for the analysis of large batches of samples. Our results confirmed the formation of ketene when VEA was vaped. The production of ketene increased with repeat puffs and showed a correlation to temperatures (200 to 500 °C) measured within vaping devices. Device battery power strength, which affects the heating temperature, plays an important role in ketene formation. In addition to ketene, the organic oxidant duroquinone was also obtained as another thermal degradation product of VEA. Ketene was not detected when vitamin E was vaped under the same conditions, confirming the importance of the acetate group for its generation.

None of transitional lipid-based drug delivery systems (LBDDS) includes compositions containing one lipid and one water-soluble surfactant that form stable microemulsions. The conversion of liquid LBDDS to solid LBDDS has been limited by low drug loading. Previously, we have developed drug solid microemulsions containing one lipid and TPGS (a water-soluble surfactant) that achieved high drug loading and remarkably increased oral bioavailability. This study aimed to test if binary lipid systems (BLS), composed of one lipid and one water-soluble surfactant that form stable self-emulsifying microemulsions, is not an exclusive but widely applicable type of LBDDS for other lipids and surfactants and evaluate the influences of chemical structures of lipids and surfactants on microemulsions and solid microemulsions. We systemically identified new BLS by using a library of lipids and surfactants. Propylene glycol diesters and glycerol triesters were favorable for forming stable microemulsions with Tween 80, Cremophor EL, or TPGS. To the best of our knowledge, this is the first report exploring and confirming that the BLS is a new addition to traditional LBDDS, provides a promising option for researchers, and has the potential to increase drug loading to facilitate the development of solid microemulsions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus ® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer., Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system., Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was >65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (** p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo., Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer., Competing Interests: Professor Dae Hwan Shin reports a pending patent “TPGS/Soluplus Micelles containing olaparib and rapamycin, and uses thereof”. The authors report no other conflicts of interest in this work., (© 2024 Shin et al.)

Take your vitamins, or don't? Vitamin E is one of the few lipophilic vitamins in the human diet and is considered an essential nutrient. Over the years it has proven to be a powerful antioxidant and is commercially used as such, but this association is far from linear in physiology. It is increasingly more likely that vitamin E has multiple legitimate biological roles. Here, we review past and current work using neutron and X-ray scattering to elucidate the influence of vitamin E on key features of model membranes that can translate to the biological function(s) of vitamin E. Although progress is being made, the hundred year-old mystery remains unsolved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12-200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The synergistic effect of surfactant compounding on performance can be leveraged to enhance product application performance. An investigation of the surface tension and emulsification properties revealed the complex synergistic effect of the composite system comprising lauryl glucoside (LG) and lauryl glycoside sulfosuccinate (LG-SS). The composite system was used as an emulsifier for vitamin E (VE) emulsification. VE nanoemulsions with high VE content were successfully prepared. The nanoemulsion appears homogeneous and transparent and has an average size of approximately 200 nm. It has better temperature and centrifugal stability, an antioxidant capacity 2.89 times that of untreated VE, and is not easily oxidized and deactivated. In this study, we successfully constructed a complex system of LG and its derivatives and applied it to VE emulsification - this is a step toward expanding the effective application of glycosides and their derivative composite systems in food, pharmaceutics, and other industries., (© 2024 Wiley-VCH GmbH.)

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1 nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24 h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Colorectal cancer (CRC) is the third most prominent cancer worldwide, and the second leading cause of cancer death. Poor outcomes and limitations of current treatments fuel the search for new therapeutic options. Curcumin (CUR) is often presented as a safer alternative for cancer treatment with a staggering number of molecular targets involved in tumor initiation, promotion, and progression. Despite being promising, its therapeutic potential is hindered due to its hydrophobic nature. Hence, the ongoing development of optimal delivery strategies based on nanotechnology, such as polymeric micelles (PMs), to overcome issues in CUR solubilization and delivery to tumor cells. In this sense, this study aimed to optimize the development and stability of CUR-loaded P123:F127:TPGS PMs (PFT:CUR) based on the thin-film approach and evaluate their therapeutic potential in CRC. Overall, the results revealed that the solubility of CUR was improved when room temperature was used to hydrate the film. The PFT-CUR hydrated at room temperature presents an average hydrodynamic diameter of 15.9 ± 0.3 nm with a polydispersity index (PDI) of 0.251 ± 0.103 and a zeta potential of -1.5 ± 1.9 mV, and a 35.083 ± 1.144 encapsulation efficiency (EE%) and 3.217 ± 0.091 drug loading (DL%) were observed. To ensure the stability of the optimized PFT-CUR nanosystems, different lyophilization protocols were tested, the use of 1% of glycine (GLY) being the most promising protocol. Regarding the critical micellar concentration (CMC), it was shown that the cryoprotectant and the lyophilization process could impact it, with an increase from 0.064 mg/mL to 0.119 mg/mL. In vitro results showed greater cytotoxic effects when CUR was encapsulated compared to its free form, yet further analysis revealed the heightened cytotoxicity could be attributed to the system itself. Despite challenges, the developed CUR-loaded PM shows potential as an effective therapeutic agent for CRC. Nonetheless, the system must undergo refinements to enhance drug entrapment as well as improve overall stability., Competing Interests: The authors have no conflicts of interest.

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures., (© 2024. The Author(s).)

The purpose of this study was to investigate the impact of different functional stabilizers on in vitro/in vivo drug performances after oral administration of drug nanocrystals. Quercetin nanocrystals (QT-NCs) respectively stabilized by five types of functional stabilizers, including hydroxypropyl methyl cellulose E15 (HPMC E15), poloxamer 407 (P407), poloxamer 188 (P188), D-α-tocopherol polyethylene glycol succinate (TPGS), and glycyrrhizin acid (GL), were fabricated by wet media milling technique. The particle size, morphology, physical state, drug solubility, drug dissolution in vitro , and orally pharmacokinetic behaviors of all QT-NCs were investigated. All QT-NCs with similar particle size about 200 nm were obtained by controlling milling speed and milling time. No significant differences in particles shape and crystalline nature were found for QT-NCs stabilized by different functional stabilizers. But the solubility and dissolution of QT-NCs were significantly influenced by the different functional stabilizers. The AUC 0∼ t of all QT-NCs after oral administration was in the following order: QT-NCs/P188 ≈ QT-NCs/HPMC E15 > QT-NCs/GL > QT-NCs/P407 ≈ QT-NCs/TPGS, and the C max showed an order of QT-NCs/P407 > QT-NCs/P188 ≈ QT-NCs/GL > QT-NCs/HPMC E15 > QT-NCs/TPGS. Both of QT-NCs/P407 and QT-NCs/TPGS exhibited faster oral absorption with T max at 0.5 h and 0.83 h, respectively, while the other three QT-NCs (QT-NCs/P188, QT-NCs/GL and QT-NCs/HPMC E15) showed a relatively slow absorption with same T max at 5.33 h. The longest MRT 0∼ t (11.72 h) and t 1/2z (32.22 h) were observed for QT-NCs/HPMC E15. These results suggested that the different functional stabilizers could significantly influence on drug solubility, drug dissolution in vitro and orally pharmacokinetic behavior of QT-NCs, and it is possible to alter the drug dissolution in vitro , oral absorption and drug retention in vivo by changing the type of functional stabilizers in NCs preparation.

Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/β-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59 nm and -25.54±0.11 mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, β-catenin and T-cell factor (TCF) expressions at protein level in the wnt/β-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Chemically cross-linked hydrogel nanoparticles (HGNPs) offer enhanced properties over their physical counterparts, particularly in drug delivery and cell encapsulation. This study applied pH-thermal dual responsive bio-adhesive HGNPs for dual complexation and enhanced the controlled release and bioavailability of cisplatin (CDDP) and Vitamin E (VE) drugs. The CDDP was loaded into the HGNPs via chemical conjugation with the carboxyl groups in the HGNPs surface by soy polysaccharides (SSPS). At the same time, the host-guest interaction complexed the VE through the β-cyclodextrin (β-CD). The HGNPs showed a uniform HGNPs size distribution of 90.77 ± 14.77 nm and 81.425 ± 13.21 nm before and after complexation, respectively. The FTIR, XRD, XPS, and zeta potential confirmed the conjugation. The cumulative release percent of CDDP reached 98 % at pH 1.2, while <45 % was released at pH 7.4. Our HGNPs enhance the incorporation of CDDP by substituting its chlorides with carboxyl groups of the SSPS; the loading of CDDP and VE was 15 ± 0.33 and 11.32 ± 0.25 wt%, respectively. Moreover, the CDDP and VE also released slower from the HGNPs at 25 °C than at 37 °C and 42 °C. The (VE/CDDP)-loaded HGNPs exhibited longer circulation time in vivo than free CDDP and free VE suspension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explored the mechanism of interaction of pH-shifting combined ultrasonication and its effect on soybean lipophilic proteins (SLP) and the potential of modified SLP as the carrier for vitamin E (VE) and quercetin (QU). The spectroscopy results revealed that both VE and QU changed the SLP conformation and exposed hydrophobic groups. The loading rates of VE and QU by SLP with alkaline pH-shifting combined with ultrasonication (300 w,20 min) were 86.91% and 75.99%, respectively. According to the antioxidant analysis, with an increase in the ultrasonication power, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging capacity of the samples increased, where the DPPH and ABTS radical scavenging capacity of sample SQV-6 were 70.90% and 63.43%, respectively. The physicochemical properties, microstructure, and stability of the SLP-VE-QU complex improved significantly. Overall, the present findings broadened the application of simple structural carriers for co-encapsulating functional factors., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024. Published by Elsevier Ltd.)

In this study, vitamins C and E were simultaneously encapsulated in water-in-oil-in-water (W/O/W) emulsion-filled sodium alginate (SA) hydrogel beads, as well as the effects of SA concentrations (0.5%, 1.0%, 1.5%, and 2.0%) on the structures and lipolysis the of hydrogel beads were investigated. With increasing SA concentration, the beads showed larger sizes, denser structures and better textures. The droplets tightly penetrated the gel network at high SA concentrations. Digestion behavior revealed the disintegrated intramolecular structure at low SA concentrations. The beads with 0.5% SA were fragmented, losing the initial shape during digestion in the intestinal fluid. Additionally, lipid phases were released as W/O/W and O/W emulsion droplets after digestion. However, the high SA concentration-containing beads exhibited a well-preserved morphological structure after digestion, and the release profiles of lipid phase were mainly O/W emulsion droplets. Furthermore, vitamins C and E encapsulated in the beads exhibited high bioaccessibility (vitamin C: 90.20% and vitamin E: 95.19%)., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emulsification potential of plant-based emulsifiers, that is, pea (PPI) and lentil (LPI) proteins (4%), corn arabinoxylans (CAX, 1%), and legume protein-arabinoxylan mixtures (4% proteins + 0.15 or 0.9% CAX), was evaluated by assessing: the surface tension and potential of emulsifiers, emulsifier antinutritional contents, emulsion droplet size, emulsion physical stability, and vitamin E bioaccessibility from 10% oil-in-water emulsions. Tween 80 (2%) was used as a control. All emulsions presented small droplet sizes, both fresh and upon storage, except 4% LPI + 0.9% CAX emulsion that exhibited bigger droplet sizes (d(4,3) of approximately 18.76 μm vs 0.59 μm for the control) because of droplet bridging. Vitamin E bioaccessibility from emulsions stabilized with the combination of 4% PPI and either 0.15% or 0.9% CAX (28 ± 4.48% and 28.42 ± 3.87%, respectively) was not significantly different from that of emulsions stabilized with Tween 80 (43.56 ± 3.71%), whereas vitamin E bioaccessibility from emulsions stabilized with individual emulsifiers was significantly lower., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of Pickering emulsions for biocatalysis is gaining increased attention. However, the extensive application is greatly limited due to the enzyme inactivation. Herein, a biocatalytic Pickering emulsion with high-performance utilizing cellulose nanocrystals immobilized lipases (CNCs-Lps) particles as stabilizer is advanced and applied for the synthesis of Vitamin E nicotinate. CNCs-Lps display high activity and reusability due to the construction of biocatalytic microreactor in the O/W emulsion system. The yield of vitamin E nicotinate ester reached up to 83 %. More importantly, the CNCs-Lps can be reused due to the similar principles to microreactors in Pickering emulsions. Reusability test showed that the CNCs-Lps could be recovered from the emulsion system by centrifugation and the yield of vitamin E nicotinate retains 78 % of initial value after five cycles, demonstrating overwhelming advantage than the fair counterpart with free lipases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 μg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 μg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.

The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of -32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.

Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Vitamin E encapsulation into biopolymer-based microparticles, obtained by spray-drying technology, was proposed to improve the encapsulation efficiency and the controlled release of fat-soluble vitamin. Binary and ternary blends of pectin, modified chitosan and modified starch, modified starch + modified chitosan, modified starch + pectin, modified chitosan + pectin and modified starch + modified chitosan + pectin ((0.33, 0.33, 0.33), (0.70, 0.15, 0.15), (0.15, 0.70, 0.15) and (0.15, 0.15, 0.70)) were proposed to produce and evaluate different carrier-based delivery systems. Vitamin E-loaded microparticles and empty microparticles were created with a product yield between 9 and 49 %. The mean diameter among all microparticles varied between 3.74 ± 0.02 and 421 ± 21 μm (differential volume distribution). Oval, spherical or irregular microparticles, with a variable morphology from a smooth to a high rough surface structure, with concavities, were produced. All vitamin E-loaded microparticles exhibited an encapsulation efficiency higher than 70 %. The slower vitamin E controlled release was observed from microparticles composed by modified chitosan (>36 h), while the faster release was achieved from microparticles individually composed by pectin (39 min). In general, the Fickian diffusion is the main release mechanism involved in the microparticles produced with modified chitosan, other formulations combine also other mechanisms such as swelling., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 μm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as drugs. Here, we reported for the first time the preparation and characterization of NCs consisting of chondroitin sulfate (CS)-based shells and liquid oil cores. For this purpose, two amphiphilic CS derivatives (AmCSs) were obtained by grafting the polysaccharide chain with octadecyl or oleyl groups. AmCS-based NCs were prepared by an ultrasound-assisted emulsification of an oil phase consisting of a mixture of triglyceride oil and vitamin E in a dispersion of AmCSs. Dynamic light scattering and cryo-transmission electron microscopy showed that the as-prepared core-shell NCs have typical diameters in the range of 30-250 nm and spherical morphology. Since CS is a strong polyanion, these particles have a very low surface potential, which promotes their stabilization. The cytotoxicity of the CS derivatives and CS-based NCs and their impact on cell proliferation were analyzed using human keratinocytes (HaCaTs) and primary human skin fibroblasts (HSFs). In vitro studies showed that AmCSs dispersed in an aqueous medium, exhibiting mild cytotoxicity against HaCaTs, while for HSFs, the harmful effect was observed only for the CS derivative with octadecyl side groups. However, the nanocapsules coated with AmCSs, especially those filled with vitamin E, show high biocompatibility with human skin cells. Due to their stability under physiological conditions, the high encapsulation efficiency of their hydrophobic compounds, and biocompatibility, AmCS-based NCs are promising carriers for the topical delivery of lipophilic bioactive compounds., Competing Interests: The authors declare no conflict of interest.

Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer. Targeting the overexpressed anti-apoptotic Bcl-2 protein in breast cancer, Gefitinib (GEF), an EGFR (Epidermal Growth Factor Receptor) inhibitor, emerges as a potential solution. This study focuses on designing Gefitinib-loaded polymeric mixed micelles (GPMM) using poloxamer 407 and TPGS (D-alpha tocopherol PEG 1000 succinate) for breast cancer therapy. In silico analyses unveil strong interactions between GEF- Bcl-2 and TPGS-Pgp-2 receptors, indicating efficacy against breast cancer. Molecular dynamics simulations offer insights into GEF and TPGS interactions within the micelles. Formulation optimization via Design of Experiment ensures particle size and entrapment efficiency within acceptable ranges. Characterization tools such as zeta sizer, ATR-FTIR, XRD, TEM, AFM, NMR, TGA, and DSC confirms particle size, structure, functional groups, and thermodynamic events. The optimized micelles exhibit a particle size of 22.34 ± 0.18 nm, PDI of 0.038 ± 0.009, and zeta potential of -0.772 ± 0.12 mV. HPLC determines 95.67 ± 0.34% entrapment efficiency and 1.05 ± 0.12% drug loading capacity. In-vitro studies with MDA-MB-231 cell lines demonstrate enhanced cytotoxicity of GPMM compared to free GEF, suggesting its potential in breast cancer therapy. Cell cycle analysis reveals apoptosis induction through key apoptotic proteins. Western blot results confirm GPMM's ability to trigger apoptosis in MDA-MB-231 cells by activating caspase-3, Bax, Bcl-2, and Parp. In conclusion, these polymeric mixed micelles show promise in selectively targeting cancer cells, warranting future in-vivo studies for optimized clinical application against breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release. The system was loaded with melatonin and cyclosporin A, neuroprotective compounds to be delivered to the posterior eye segment. Citric acid and heating at different times and temperatures were exploited as crosslinking approach, giving the possibility to tune swelling, micelles release and drug release. The biocompatibility of the platform was confirmed by HET-CAM assay. Ex vivo studies on isolated porcine ocular tissues, conducted using Franz cells and two-photon microscopy, demonstrated the potential of the xanthan gum-based platform and enlightened micelles penetration mechanism. Finally, the sterilization step was approached, and a process to simultaneously crosslink and sterilize the platform was developed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The groundbreaking discovery of vitamin E by Evans and Bishop in 1922 was an important milestone in vitamin research, inspiring further investigation into its crucial role in both human and animal nutrition. Supplementing vitamin E has been proved to enhance multiple key physiological systems such as the reproductive, circulatory, nervous and muscular systems. As the main antioxidant in the blood and on a cellular level, vitamin E maintains the integrity of both cellular and vascular membranes and thus modulates the immune system. This overview showcases important and innovative routes for synthesizing vitamin E on a commercial scale, provides cutting-edge insights into formulation concepts for successful product form development and emphasizes the importance and future of vitamin E in healthy and sustainable animal nutrition., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Vitamin E (VE) microencapsulation using a green surfactant emulsifier not only protects the active substance and is also environmentally friendly. In this study, we used alcohol ether glycoside as an emulsifier to prepare VE microcapsules using the biological macromolecule Zein and various polysaccharides. The resulting nano microcapsules exhibited a spherical structure, stable morphology, uniform size, and a >90% encapsulation efficiency. They also had good thermal stability and slow-release properties. Of these, xanthan gum/Zein-VE microcapsules were superior, with antioxidant properties up to 3.05-fold higher than untreated VE. We successfully developed VE nano microcapsules that meet eco-friendly and sustainable requirements, which may have applications in the food and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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, β-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.

In this work, soybean lecithin (LC) was used to modify β-cyclodextrin (β-CD) with hydrophobic fat chains to become amphiphilic (LC-CD), and vitamin E (VE) was encapsulated in former modified β-CD complexes (LC-CD-VE), the new Pickering emulsions stabilized by LC-CD-VE and LC-CD complexes for the delivery of β-carotene (BC) were created. The surface tension, contact angle, zeta potential, and particle size were used to assess the changes in complexes nanoparticles at various pH values. Furthermore, LC-CD-VE has more promise as Pickering emulsion stabilizer than LC-CD because of the smaller particle size (271.11 nm), proper contact angle (58.02°), and lower surface tension (42.49 mN/m). The interactions between β-cyclodextrin, soybean lecithin, and vitamin E were confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). The durability of Pickering emulsions was examined at various volume fractions of the oil phase and concentrations of nanoparticles. Compared to the emulsion stabilized by LC-CD, the one stabilized by LC-CD-VE showed superior storage stability. Moreover, for the delivery of BC, Pickering emulsions stabilized by LC-CD and LC-CD-VE can outperform bulk oil and Tween 80 stabilized emulsions in terms of UV light stability, storage stability, and bioaccessibility. This work could offer fresh perspectives on stabilizer alternatives for Pickering emulsion delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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-PEG 2000 /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., (© 2024 Wiley‐VCH GmbH.)

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 (T m,α ), 35.1 °C ( [Formula: see text] ) and 45.7 °C (T m,β ). From a process perspective, the only possibility to generate products coated with formulations composed of trilaurin is by setting thermal operational conditions above T m,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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To develop a robust drug-delivery system using multi-arm amphiphilic block copolymers for enhanced efficacy in cancer therapy. Materials & methods: Two series of amphiphilic polymer micelles, PEG-b-PCL m and PEG-b-PCL m /TPGS, were synthesized. Doxorubicin (DOX) loading into the micelles was achieved via solvent dialysis. Results: The micelles displayed excellent biocompatibility, narrow size distribution, and uniform morphology. DOX-loaded micelles exhibited enhanced antitumor efficacy and increased drug accumulation at tumor sites compared with free DOX. Additionally, 4A-PEG 47 -b-PCL 21 /TPGS micelles effectively suppressed drug-resistant MCF-7/ADR cells. Conclusion: This study introduces a novel micelle formulation with exceptional serum stability and efficacy against drug resistance, promising for cancer therapy. It highlights innovative strategies for refining clinical translation and ensuring sustained efficacy and safety in vivo .

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., Competing Interests: Declaration of competing interest Authors declare there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In Alzheimer's disease (AD), amyloid beta (Aβ 1-42 ) aggregate formation and neurofibrillary tangles are major pathological hallmarks which are related to neurodegeneration in the brain. To alleviate Aβ 1-42 fibrils toxicity vitamin E derivative tocopheryl polyethylene glycol succinate (TPGS) was conjugated with polyamidoamine (PAMAM) dendrimer through carbodiimide reaction to synthesize TPGS-PAMAM. This TPGS-PAMAM was employed to entrap neuroprotective agent piperine (PIP) through an anti-solvent technique to prepare PIP-TPGS-PAMAM. The dendrimer conjugate was prepared to reduce Aβ 1-42 induced neurotoxicity and increase acetylcholine levels in AD mice models. The synthesis of dendrimer conjugate was characterized through proton nuclear magnetic resonance (NMR) and Trinitrobenzene sulphonic acid assay (TNBS). Physical characterization of dendrimers conjugates were done through various spectroscopic, thermal and microscopy based techniques. PIP-TPGS-PAMAM showed 43.25 nm particle size with PIP percentage encapsulation efficiency of 80.35%. Further Aβ 1-42 fibril disaggregation effect of nanocarrier was evaluated using Thioflavin-T (ThT) assay and circular dichroism (CD). The neuroprotection studies for PIP-TPGS-PAMAM was evaluated against neurotoxicity induced using Aβ 1-42 intracerebroventricular (ICV) injected in Balb/c mice. The group of mice administered with PIP-TPGS-PAMAM exhibited an increase in the proportion of random alternations in T-maze test and novel object recognition test (NORT) exhibited an increase in working memory cognitive functions. The biochemical and histopathological analysis revealed PIP-TPGS-PAMAM treated groups enhanced acetylcholine levels, reduced ROS and Aβ 1-42 content significantly. Our findings imply that PIP-TPGS-PAMAM enhanced memory and reduced cognitive deficit in mice brain induced by Aβ 1-42 toxicity.

In the present study, D-α-Tocopherol polyethylene glycol 1000 succinate-based self-microemulsifying drug delivery systems (TPGS-SMEDDS) were introduced to enhance the solubility and stability of luteolin. The ternary phase diagrams were constructed to obtain the maximum area of microemulsion and suitable formulations of TPGS-SMEDDS. The particle size distribution and polydispersity index of selected TPGS-SMEDDS were analyzed to be less than 100 nm and 0.4, respectively. The thermodynamic stability results suggested that the TPGS-SMEDDS was stable during the heat-cool and freeze-thaw cycle. Moreover, the TPGS-SMEDDS exhibited excellent encapsulation capacity (51.21 ± 4.39 to 85.71 ± 2.40%) and loading efficiency (61.46 ± 5.27 to 102.86 ± 2.88 mg/g) to luteolin. In addition, the TPGS-SMEDDS showed an admirable vitro release ability with a ratio of more than 88.40 ± 1.14% for luteolin in 24 h. Therefore, TPGS-based SMEDDS might provide an effective role for the oral administration of luteolin and holds promise as a potential delivery for poorly soluble bioactive compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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 IC 50 against MCF-7 (4.51 µg/mL) and T47D (8.22 µg/mL) cancer cells. When T47D cells were treated with IC 50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC 50 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., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Ahmed et al.)

Oils and fats are important ingredients for food and pharmaceutical industries. Their main compounds, such as triacylglycerols (TAG), are responsible for determining their physical properties during food storage and consumption. Lipid-rich foods are also sources of minority compounds, which is the case of vitamin E, mainly represented by (±)-α-tocopherol. These compounds can interact with the main lipid molecules in food formulation leading to modification on lipids' physicochemical properties during processes, storage, as well as during digestion, possibly altering their nutritional functionalities, which is the case of vitamin E antioxidant abilities, but also their solubility in the systems. In this case, the study of the phase-behavior between (±)-α-tocopherol and lipid compounds can elucidate these physicochemical changings. Therefore, this work was aimed at determining the solid-liquid equilibrium (SLE) of binary mixtures of TAG (tripalmitin, triolein and tristearin) and (±)-α-tocopherol including the complete description of their phase diagrams. Melting data were evaluated by Differential Scanning Calorimetry, Microscopy, X-Ray Diffraction, and thermodynamic modeling by using Margules, UNIFAC, and COSMO-SAC models. Experimental results showed that systems presented a monotectic-like behavior, with a significant decreasing in TAG melting temperature by the addition of (±)-α-tocopherol. This high affinity and attractive strengths between these molecules were also observed by thermodynamic modeling, whose absolute deviations were below 2 %. Micrographs and X-ray diffraction evidenced the possible formation of solid solutions. Both behaviors are interesting by avoiding phase separation on food in solid and liquid phases, possibly improving the antioxidant role the (±)-α-tocopherol in lipid-base systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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. IC 50 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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

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 IC 50  = 3 µM. Furthermore, regarding MCF-7, F1 was shown to be the most potent and protective among all the tested formulations with an IC 50  = 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

Objective: Fenofibrate (FNF), an anti-hyperlipidemic agent, suffers from poor water solubility (0.000707mg/ml) and belongs to class II drug as per BCS, shows a slow dissolution rate. The current investigation aimed to fabricate a fast-dissolving tablet of FNF (not available in the commercial market) using solid dispersion technique employing Vitamin E-D-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as molecular biomaterial to enhance dissolution rate and reduce the time required to reach the systemic circulation., Materials and Methods: Firstly, carrier material was selected based on the release study via preparing solid dispersion using the melting method, and prepared solid dispersion was characterized. Secondly, fast-dissolving tablets from solid dispersion were fabricated using the direct compression tool and characterized for X-ray diffraction (XRD) pattern, friability, hardness, content uniformity, weight variation and in vitro disintegration test., Results: The X-ray diffraction study confirmed the successful formation of solid dispersion using vitamin E TPGS by analyzing the change in physical state. The fabricated solid dispersion exhibited higher drug content than a physical mixture of FNF. An excipient interference study was also performed in methanol and 0.75% w/v sodium lauryl sulphate. It revealed no significant alterations in the absorption peak of FNF as analyzed using UV spectroscopy at 287nm. In addition, water absorption ratio phase solubility and wetting time were also assessed. In -vitro release of FNF from developed tablets was found significantly higher (93.23%±3.11; p<0.001) as compared to prepared compressed tablet of pure FNF (12.21±2.34%). The dissolution rate was also determined, and data were then kept to various kinetic models such as zero-order chemical kinetic, first-order chemical kinetic, Hixon-Crowell and Higuchi chemical kinetic., Conclusion: A complete and sequential in vitro and physicochemical characterization of developed formulation was carried out to set-up improved and effective treatment for high blood cholesterol., (Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

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 (O 2 ) 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 (N 2 ) 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 O 2 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. O 2 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.

Vitamin E (VE) is currently an approved antioxidant to improve the oxidation stability of highly crosslinked ultrahigh molecular weight polyethylene (UHMWPE) insert used commercially in total joint arthroplasty. However, the decrease in crosslink density caused by VE reduces wear resistance of UHMWPE, showing an uncoordinated challenge. In this work, we hypothesized that D-sorbitol (DS) as a secondary antioxidant can improve the antioxidant efficacy of VE on chemically crosslinked UHMWPE. The combined effect of VE and DS on oxidation stability of UHMWPE was investigated at a set of controlled hybrid antioxidant content. The hybrid antioxidant strategy showed significantly synergistic enhancement on the oxidation stability of chemically crosslinked UHMWPE compared with the single VE strategy. More strikingly, the crosslink density of the blends with hybrid antioxidants stayed at a high level since DS is not sensitive to crosslinking. The relationships between oxidation stability, mechanical properties, crosslink density, and crystallinity were investigated, by which the clinically relevant overall performance of UHMWPE was optimized. This work provides a leading-edge design mean for the development of joint bearings., (© 2022 Wiley Periodicals LLC.)