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The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund's Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. [ABSTRACT FROM AUTHOR]

Yujuan Mao,1,* Tianjiao Hao,2,* Hongxiu Zhang,2,* Xiaofei Gu,2 Jing Wang,1 Feifei Shi,1 Xiaolan Chen,1 Liuna Guo,1 Jie Gao,1 Yan Shen,2 JinLin Zhang,3 Shenglan Yu4 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Jiangsu Institute for Food and Drug Control, Nanjing, Jiangsu Province, 210019, People’s Republic of China; 4College of Animal Medicine, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shenglan Yu; JinLin Zhang, Email slyu70@126.com; zjluser@126.comIntroduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.Keywords: eprinomectin, mixed micelles, transdermal delivery, pharmacokinetics

Chengyang Dian,1 Zebin Qian,1 Mengnan Ran,1 Xiong Yan,1 Linghui Dian1,2 1School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Dongguan Key Laboratory of Screening and Research of Anti-Inflammatory Ingredients in Chinese Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of ChinaCorrespondence: Linghui Dian, School of Pharmaceutical Sciences, Guangdong Medical University, Xincheng Road 1, Dongguan, 523808, People’s Republic of China, Tel/Fax +86769 22896560, Email 605911308@qq.comBackground: 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. Keywords: docetaxel, mixed micelles, resistant breast cancer, oral delivery, bioavailability, mice

New hexadecylpiperidinium surfactants, containing one or two butylcarbamate fragments, were synthesized. The antimicrobial activity, toxicity, aggregation behavior in aqueous solutions, and solubilization capacity of these surfactants towards the hydrophobic drug ibuprofen were characterized. These surfactants demonstrated a high antimicrobial activity against a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative strains, as well as fungi. By forming mixed-micellar compositions of the cationic surfactant 1-CB(Bu)-P-16 and the nonionic surfactant Brij®35, highly functional and low-toxic formulations were obtained. Furthermore, the transition from mixed micelles to niosomes was accomplished, enhancing their potential as drug delivery systems. Niosomes were found to be less toxic compared to mixed micelles, while also increasing the solubility of ibuprofen in water. The modification of niosomes with cationic surfactants made it possible to increase the stability of the system and improve the solubility of the drug. The data obtained indicate that these new carbamate-containing hexadecylpiperidinium surfactants have significant potential in biomedical applications, particularly in the formulation of advanced drug delivery systems. [ABSTRACT FROM AUTHOR]

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC. [ABSTRACT FROM AUTHOR]

Phospholipase A2 (PLA2) is a superfamily of phospholipase enzymes that dock at the water/oil interface of phospholipid assemblies, hydrolyzing the ester bond at the sn-2 position. The enzymatic activity of these enzymes differs based on the nature of the substrate, its supramolecular assemblies (micelle, liposomes), and their composition, reflecting the interfacial nature of the PLA2s and requiring assays able to directly quantify this interaction of the enzyme(s) with these supramolecular assemblies. We developed and optimized a simple, universal assay method employing the pH-sensitive indicator dye bromothymol blue (BTB), in which different POPC (3-palmitoyl-2-oleoyl-sn-glycero-1-phosphocholine) self-assemblies (liposomes or mixed micelles with Triton X-100 at different molar ratios) were used to assess the enzymatic activity. We used this assay to perform a comparative analysis of PLA2 kinetics on these supramolecular assemblies and to determine the kinetic parameters of PLA2 isozymes IB and IIA for each supramolecular POPC assembly. This assay is suitable for assessing the inhibition of PLA2s with great accuracy using UV-VIS spectrophotometry, being thus amenable for screening of PLA2 enzymes and their substrates and inhibitors in conditions very similar to physiologic ones. [ABSTRACT FROM AUTHOR]

Micelles of different types and properties are basically formed by the assembly of surfactants. The conditions for the formation of micelles, their shapes, sizes and morphologies are also different, and are discussed for surfactants, block copolymers and ionic liquids in the present article. Theories by Debye and others, Markov chain model, ladder model of micelle growth are employed to understand in detail the thermodynamics of micelles and mixed micelles formation. Apart from these, other concepts like effect of additives on micelle formation, application of polymeric, multicompartment micelles in drug delivery, fundamentals of formation of single and double critical micelle concentration and computer simulation methods for amphiphile aggregation are reviewed in the present study. [ABSTRACT FROM AUTHOR]

Vitamin D is an essential micronutrient; it is necessary for human well-being, including brain and heart health; its deficiency is widespread and can lead to fatal diseases. Daily consumed foods are enriched and fortified with vitamin D; still, adequate bioavailability and safe delivery are significant issues. In the food system, due to unfavorable conditions, vitamin D loses its nature and functionality; likewise, it is fat-soluble and can't be incorporated into juices and soft drinks. Due to the acidic nature of the gastric environment, the timely release and adequate bioavailability of vitamin D is also hampered. Therefore, the most challenging and critical issue is the application of techniques to safeguard vitamin D for its optimum functionality. Recently food researchers and nutritionists are developing innovative methods using nanotechnology to ensure the safety of vitamin D, its timely release and absorbance during digestion. This review reflects valuable data, precisely the effectiveness of recently developed nano-based methods on vitamin D's sustainability, retention, and bioavailability, including nano-encapsulation, nanoemulsion, mixed micelles, complexation, and Conjugation. This manuscript also discusses some of the important clinical trialed based health benefits of vitamin D, summarizes the most recent techniques developed, and demonstrates understanding of novel methods and future developments. [ABSTRACT FROM AUTHOR]

This research highlights the efficacy of mixed micellar systems as an innovative chemical formulation for improving the binding properties of active pharmaceutical drugs. The formulations based on the mole fraction were utilized for preparing mixed micelles with anionic sodium dioctyl sulfosuccinate (AOT) and sodium dodecyl sulphate (SDS). DLS measurements demonstrated the formation of small micelles and mixed micelles in SDS‐AOT combinations. A UV absorbance investigation demonstrated the effectiveness of the SDS‐AOT mixed micelles for determining the binding constant (Kb) and mean ion occupancy (i0) of the anticonvulsant gabapentin (GBP) drug. Kb values increased, but the occupancy (i) of GBP per micelle decreased by decreasing the mole fraction (α) of SDS from αSDS 0.9 to 0.1, predicting a shift in occupancy of drugs from the Palisade to the Stern layer. To get a better comprehension of micellization behavior and preferential interaction of the drugs under study, molecular docking studies were performed. According to the docking studies, the GBP displayed significant binding in the presence of SDS‐AOT when compared to pure SDS and AOT molecules. Ultimately, in pharmaceutical applications, mixed micelle played an important role in enhancing the binding and encapsulation efficiency of drugs. [ABSTRACT FROM AUTHOR]

Abstract Background Docetaxel (DTX) finds extensive use in treating various cancers, but its limited solubility, side effects, and multi-drug resistance (MDR) hinder its effectiveness. To enhance DTX's properties, the study aimed to formulate DTX-loaded mixed micelles (MMs) and evaluate their anticancer potential using Quality by Design (QbD) approach. Using solvent evaporation, DTX-loaded MMs were prepared and optimized via a 32 full factorial design. Results The optimized formulation (R5) displayed a % entrapment efficiency (%EE) of 74.81 ± 4.27%, % drug loading capacity (%DLC) of 29.27 ± 0.70%, and mean particle size (MPS) of 71.4 ± 1.24 nm. TEM images confirmed well-dispersed spherical MMs. Analytical studies (IR, DSC, and P-XRD) showed no adverse drug-excipient interactions. The MMs were converted into vacuum foam-dried (VFD) products for enhanced stability. The optimized VFD products exhibited low residual moisture, rapid reconstitution, consistent drug content, and high %EE. Notably, sustained drug release from the VFD product reduced hemolysis and in vitro cytotoxicity against B16F10 melanoma cells. Conclusion This study creatively tackled DTX's challenges through targeted MM development, transformed them into VFD products, demonstrating the potential for melanoma treatment. The QbD approach ensures the formulation’s safety, efficacy, and quality, underscoring the promising VFD technology and multifunctionality of mixed micelles. Graphical abstract

Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG- b -P(GMA- ss -DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG- b -P(GMA- ss -DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen (1O 2) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer- ss -DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DTX) finds extensive use in treating various cancers, but its limited solubility, side effects, and multi-drug resistance (MDR) hinder its effectiveness. To enhance DTX's properties, the study aimed to formulate DTX-loaded mixed micelles (MMs) and evaluate their anticancer potential using Quality by Design (QbD) approach. Using solvent evaporation, DTX-loaded MMs were prepared and optimized via a 32 full factorial design. Results: The optimized formulation (R5) displayed a % entrapment efficiency (%EE) of 74.81 ± 4.27%, % drug loading capacity (%DLC) of 29.27 ± 0.70%, and mean particle size (MPS) of 71.4 ± 1.24 nm. TEM images confirmed well-dispersed spherical MMs. Analytical studies (IR, DSC, and P-XRD) showed no adverse drug-excipient interactions. The MMs were converted into vacuum foam-dried (VFD) products for enhanced stability. The optimized VFD products exhibited low residual moisture, rapid reconstitution, consistent drug content, and high %EE. Notably, sustained drug release from the VFD product reduced hemolysis and in vitro cytotoxicity against B16F10 melanoma cells. Conclusion: This study creatively tackled DTX's challenges through targeted MM development, transformed them into VFD products, demonstrating the potential for melanoma treatment. The QbD approach ensures the formulation's safety, efficacy, and quality, underscoring the promising VFD technology and multifunctionality of mixed micelles. [ABSTRACT FROM AUTHOR]

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin–spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry. [ABSTRACT FROM AUTHOR]

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (p ≤ 0.05–0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity. [ABSTRACT FROM AUTHOR]

The aggregation behavior of mixed micellar solutions based on 2-hydroxyethylpiperidinium surfactants and nonionic surfactant Brij® 35 was investigated. The critical micelle concentrations determined by varying the component ratio suggest a negative deviation from the ideal mixing model (synergistic effect). It was demonstrated that the magnitude of the deviation from ideal mixing behavior depends on the alkyl chain length in the cationic surfactant and on the component ratio. The solubilization effect of the binary systems on hydrophobic substances was evaluated taking Orange OT dye and ibuprofen drug as examples. It was found that the piperidinium surfactants studied, both individually and in compositions containing up to 50% of the nonionic surfactant, exhibit high antimicrobial activity comparable to that of commercial antibiotics. [ABSTRACT FROM AUTHOR]

New hexadecylpiperidinium surfactants, containing one or two butylcarbamate fragments, were synthesized. The antimicrobial activity, toxicity, aggregation behavior in aqueous solutions, and solubilization capacity of these surfactants towards the hydrophobic drug ibuprofen were characterized. These surfactants demonstrated a high antimicrobial activity against a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative strains, as well as fungi. By forming mixed-micellar compositions of the cationic surfactant 1-CB(Bu)-P-16 and the nonionic surfactant Brij®35, highly functional and low-toxic formulations were obtained. Furthermore, the transition from mixed micelles to niosomes was accomplished, enhancing their potential as drug delivery systems. Niosomes were found to be less toxic compared to mixed micelles, while also increasing the solubility of ibuprofen in water. The modification of niosomes with cationic surfactants made it possible to increase the stability of the system and improve the solubility of the drug. The data obtained indicate that these new carbamate-containing hexadecylpiperidinium surfactants have significant potential in biomedical applications, particularly in the formulation of advanced drug delivery systems.

The aggregation behaviour of organic dyes and their application to produce mixed micelles with surfactants has received not much study. The critical micelle concentration (CMC) of mixed micelle was obtained by the mixture of sunset yellow (SSY) and hexadecyltrimethylammonium chloride (CTAC)/ sodium tetradecyl sulphate (STS) in an aqueous media using surface tension and conductivity methods. The maximum reduction in CMC was found at αSSY 0.5, and CMC was 0.685 mmolL−1 for SSY-CTAC and 0.784 mmol L−1 for SSY-STS. The mixed micelle for dye-surfactants exhibited significant attractive interactions of SSY with CTAC and STS through the negative interaction parameter (βm) values. The Surface excess (Γmax) and minimum area per molecule (Amin) increased with increases of αSSY 0.9 to 0.1 which indicated that more CTA + and ST¯ absorbed than SY¯ monomers in SSY–CTAC and SSY–STS. The peff values were found to be 0.169 and 0.045 for SSY-STS and 0.173–0.052 for SSY-CTAC in mixed micellar solutions between αSSY 0.9 and 0.1, respectively, indicating the formation of spherical mixed micelles. Studies using Transmission electron microscopy (TEM) and dynamic light scattering (DLS) verified the development of spherical vesicles with a diameter of 300.2 nm for SSY-CTAC and spherical micelles 85.7 nm for SSY-STS at αSSY 0.5. The Ostwald viscometer measured viscosity (η), which affected mixed micelles sizes and morphologies for mixed aggregates. In conclusion, the application of CMC in amphiphilic dye could be utilised to improve the surface activity of excipients in the applications of the textile, pharmaceutical, and food sectors. [ABSTRACT FROM AUTHOR]

The study of many membrane enzymes in an aqueous medium is difficult due to the loss of their catalytic activity, which makes it necessary to use membrane-like systems, such as reverse micelles of surfactants in nonpolar organic solvents. However, it should be taken into account that the micelles are a simplified model of natural membranes, since membranes contain many different components, a significant part of which are phospholipids. In this work, we studied impact of the main phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), on activity of the membrane enzymes using galactonolactone oxidase from Trypanosoma cruzi (TcGAL) and L-galactono-1,4-lactone dehydrogenase from Arabidopsis thaliana (AtGALDH) as examples. Effect of the structure (and charge) of the micelle-forming surfactant itself on the activity of both enzymes has been studied using an anionic surfactant (AOT), a neutral surfactant (Brij-96), and a mixture of cationic and anionic surfactants (CTAB and AOT) as examples. The pronounced effect of addition of PC and PE lipids on the activity of AtGALDH and TcGAL has been detected, which manifests as increase in catalytic activity and significant change in the activity profile. This can be explained by formation of the tetrameric form of enzymes and/or protein–lipid complexes. By varying composition and structure of the micelle-forming surfactants (AOT, CTAB, and Brij-96) it has been possible to change catalytic properties of the enzyme due to effect of the surfactant on the micelle size, lipid mobility, charge, and rigidity of the matrix itself. [ABSTRACT FROM AUTHOR]

Mixed micelles from copolymers in aqueous media have emerged as a valuable tool for producing functional polymer nanostructures with applications in nanomedicine, including drug delivery and bioimaging. In this review, we discuss the basics of mixed copolymer micelles’ design, structure, and physicochemical properties. We also focus on their utilization in biomedical applications using examples from recent literature.

We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D5–D7 were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids—compounds 3 and 4—from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D3, a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D3. Compound 3 showed similar uptake levels but transported about half as much as vitamin D3. These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3's activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D2–D7 and was also predicted to have unique biological activities. [ABSTRACT FROM AUTHOR]

The combination of herbal drugs with a topical antibacterial for managing a chronic disease like acne vulgaris has emerged lately to settle side effects and bacterial multidrug resistance. Mixed micelles (MMs) incorporated into nanogel were explored for hybrid delivery of curcumin (Cur) and fusidic acid (FA) combination presenting a multi-strategic treatment. Curcumin-fusidic acid–loaded mixed micelles (Cur-FA-MMs) were assessed for size, surface charge, compatibility, in vitro release, and encapsulation. The selected formula was further loaded into nanogel and investigated for viscosity, ex vivo permeation, and in vivo potential. Cur-FA-MMs exhibited uniform nanosized spherical morphology, and negative surface charge affording high encapsulation for both drugs with a biphasic in vitro release over a period of 48h and good colloidal stability. The attained Cur-FA-MM-loaded nanogel had optimum viscosity with remarkable permeation coefficient values nearly 2-fold that related to plain nanogel. The pharmacodynamic effect of Cur on FA was pronounced by the significant improvement of the skin's degree of inflammation, epidermal hypertrophy, and congestion in animals treated with Cur-FA-MM-loaded nanogel. In conclusion, micellar nanogel could enable the progressive effect of Cur (an antioxidant with reported antibiotic activity) on FA (antibiotic) and decrease the risk of emerging antibiotic resistance by enhancing the solubility and permeation of Cur. [ABSTRACT FROM AUTHOR]

Pharmaceutical, food, and cosmetic formulations often contain binary or ternary surfactant mixtures with synergistic interactions amongst micellar building blocks. Here, a ternary mixture of the surfactants hexadecyltrimethylammonium bromide, dodecyltrimethylammonium bromide, and sodium deoxycholate is examined to see if the molar fractions of the surfactants in the ternary mixed micellar pseudophase are determined by the interaction coefficients between various pairs of the surfactants or by their propensity to self-associate. Critical micelle concentrations (CMC) of the analyzed ternary mixtures are determined experimentally (spectrofluorimetrically using pyrene as the probe molecule). Thermodynamic parameters of ternary mixtures are calculated from CMC values using the Regular Solution protocol. The tendency for monocomponent surfactants to self-associate (lower value of CMC) determines the molar fractions of surfactant in the mixed micelle if there is no issue with the packing of the micelle building units of the ternary mixed micelle. If a more hydrophobic surfactant is incorporated into the mixed micelle, the system (an aqueous solution of surfactants) is then the most thermodynamically stabilized. [ABSTRACT FROM AUTHOR]

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water‐soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate‐co‐lauryl methacrylate], H‐[P(OEGMA‐co‐LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self‐assemble into mixed micelle‐like nanostructures in aqueous environments, whereas both systems of neat and drug‐loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications. [ABSTRACT FROM AUTHOR]

Purpose: Camptothecin has poor solubility, high systemic toxicity, and intrinsic structural instability. To deal with these challenges, present research aimed to develop camptothecin-loaded mixed micelles (CPT MMs) using TPGS and Pluronic® F108 copolymers. Furthermore, our research aimed to test in vitro anticancer activities of non-micellar verapamil and ranolazine for repurposing as coadjuvant therapy with CPT MMs in cancer. Methods: CPT MMs were fabricated by solvent evaporation method and optimized using 32 full factorial design. CPT MMs were characterized for % entrapment efficiency (%EE), mean particle size (MPS), zeta potential, surface morphology, % drug loading capacity (%DLC), in vitro drug release, and in vitro cytotoxicity and cell cycle arresting behaviors. Result: The in silico studies revealed decent camptothecin interaction with a cavity of mixed micelles (MMs). CPT MMs composition (H5) is considered optimum based on %EE (94.92 ± 2.46%), MPS (136.9 ± 1.71 nm), zeta potential (− 22.9 ± 0.87 mV), and %DLC (1.810 ± 0.02%). TEM image shows self-assembled micelles with spherical shape. CPT MMs showed sustained release profile. The drug-excipient compatibility study revealed no primary incompatibilities. The CPT MMs showed moderately higher IC50 values than camptothecin against A549 and B16F10 cells. The non-micellar verapamil and ranolazine when combined with CPT MMs at lower concentrations have resulted in substantially higher cytotoxicity. Whereas, the CPT MMs + ranolazine combination has shown higher cell cycle arresting behavior than CPT MMs + verapamil combination. Conclusion: Elaborative and molecular mechanism–based studies are further needed to validate the repurposing potential of non-micellar verapamil and ranolazine as coadjuvant with CPT MMs in cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Intraperitoneal metastasis is one of the major causes of the high mortality rate of ovarian cancer. Bufalin (BU) is an effective component of the traditional Chinese medicine Chansu that exerts antitumor effects, including metastasis inhibition. In our previous studies, we found that BU inhibited the migration and invasion of ovarian cancer cells. However, the application of BU is limited due to its insolubility, toxicity and imprecise targeting. The aim of this study was to use vitamin E succinate (VES)-grafted chitosan oligosaccharide (CSO)/arginine-glycine-aspartic acid peptide (RGD)-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles (VeC/T-RGD MMs) to deliver BU to ovarian cancer cells to inhibit intraperitoneal metastasis. Moreover, the toxicity of BU was reduced by coating it with the mixed micelles to increase its biocompatibility for practical applications. Results The BU-loaded VeC/T-RGD MMs (BU@MMs) had an average diameter of 161 ± 1.4 nm, a zeta potential of 4.49 ± 1.54 mV and a loading efficiency of 2.54%. The results showed that these micelles inhibited cell proliferation, induced apoptosis, and reduced the migration and invasion of A2780 and SKOV3 cells. Further studies indicated that BU@MMs enhanced the levels of e-cadherin and decreased the expression levels of N-cadherin, vimentin and Snail in vitro. In addition, the mixed micelles effectively enhanced the anticancer effect and inhibited intraperitoneal metastasis in intraperitoneal metastatic models. The BU@MMs exhibited fewer toxic side effects than BU, indicating better biocompatibility and biosafety for in vivo applications. Conclusions Our studies show that BU@MMs are a potential multifunctional nano-drug delivery system that can effectively inhibit the intraperitoneal metastasis of ovarian cancer.

Lung cancer is the leading cause of cancer death world-wide and its treatment remains a challenge in clinic, especially for non-small cell lung cancer (NSCLC). Thus, more effective therapeutic strategies are required for NSCLC treatment. Quercetin (Que) as a natural flavonoid compound has gained increasing interests due to its anticancer activity. However, poor water solubility, low bioavailability, short half-life, and weak tumor accumulation hinder in vivo applications and antitumor effects of Que. In this study, we developed Que-loaded mixed micelles (Que-MMICs) assembled from 1,2-distearoyl-sn-glycero-3-phosphoethanolamine–poly(ethylene glycol)–biotin (DSPE–PEG–biotin) and poly(ethylene glycol) methyl ether methacrylate–poly[2-(dimethylamino) ethyl acrylate]–polycaprolactone (PEGMA–PDMAEA–PCL) for NSCLC treatment. The results showed that Que was efficiently encapsulated into the mixed micelles and the encapsulation efficiency (EE) was up to 85.7%. Cellular uptake results showed that biotin conjugation significantly improved 1.2-fold internalization of the carrier compared to that of non-targeted mixed micelles. In vitro results demonstrated that Que-MMICs could improve cytotoxicity (IC50 = 7.83 μg/mL) than Que-MICs (16.15 μg/mL) and free Que (44.22 μg/mL) to A549 cells, which efficiently induced apoptosis and arrested cell cycle. Furthermore, Que-MMICs showed satisfactory tumor targeting capability and antitumor efficacy possibly due to the combination of enhanced permeability and retention (EPR) and active targeting effect. Collectively, Que-MMICs demonstrated high accumulation at tumor site and exhibited superior anticancer activity in NSCLC bearing mice model.

SDS/Triton X-100, a mixed anionic and non-ionic surfactant system, has been chosen to study the oxidation of aniline by Fe(III) in the presence of bipyridyl. The reaction obeys pseudo first order kinetics with respect to aniline and Fe(III). The reaction has a square dependence on the concentration of bipyridyl and inverse square dependence on hydrogen ion concentration. There is no considerable effect of Triton X-100 (TX-100) micelles on the rate of the reaction. In contrast to this observation the reaction is markedly accelerated in the presence of SDS. The effect of varying mole fraction of Triton X-100 and total surfactant concentration has been carried out in the presence of mixed micelles (SDS/TX-100) and it was found that rate decreases as mole fraction of Triton X-100 (aTX-100) increases. The extent of interaction (ß) between the surfactant molecules were also determined which could explain synergistic behavior in SDS/Triton X-100 mixed micelles. Based on kinetic observations a reaction scheme has been proposed. The applicability of the Berezin pseudo - phase model has been examined in the case where the number of equilibria comes before the rate-determining step. The values of KS determined were in good agreement with values obtained from spectrophotometric method showing the applicability of Berezin pseudo - phase model to kinetic analysis of reactions involving pre-equilibria in the presence of mixed micelles. [ABSTRACT FROM AUTHOR]

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Mixed micelles from copolymers in aqueous media have emerged as a valuable tool for producing functional polymer nanostructures with applications in nanomedicine, including drug delivery and bioimaging. In this review, we discuss the basics of mixed copolymer micelles' design, structure, and physicochemical properties. We also focus on their utilization in biomedical applications using examples from recent literature. [ABSTRACT FROM AUTHOR]

Owing to their surface active properties, surfactants have numerous applications in different fields of life. In the present research work, the solubilization of reactive red 2 (RR2) has been studied in single and mixed micellar systems (MMS) using UV-visible spectroscopy and electrical conductivity measurements. The interaction of RR2 with ionic micelles of cetylpyridinium chloride (CPC) was investigated. In order to probe the interaction of RR2 in MMS, mixtures of CPC and TX-114 (Triton X-114, a nonionic surfactant) were used. UV-visible spectroscopy has been used to obtain the degree of solubilization of RR2 in terms of the partition coefficient (Kc) and Gibbs free energy of partitioning (ΔG°p). Electrical conductivity data have been employed to detect the critical micelle concentration (CMC) of the surfactant systems in the presence of RR2 and, accordingly, to calculate the thermodynamic parameters of the micellization. From the obtained data, it is concluded that the micellization is spontaneous at all studied temperatures. Moreover, the micellization was observed to be driven by both enthalpy and entropy. The results also indicated that MMS have better solubilizing power than single micellar solutions. [ABSTRACT FROM AUTHOR]

The present work aimed to study the mixed micellar behaviour of a tri-substituted imidazolium based surface-active ionic liquid (SAIL), 1-tetradecyl-2,3-dimethylimidazolium bromide [C14bmim][Br], with a drug Nortriptyline hydrochloride (NOT) in the water/salt (Na2SO4) medium using surface tension measurements (298.15 K) alongwith conductivity measurements (298.15K–313.15K). Lower experimentally obtained cmc values compared to their ideal values suggest that the investigated amphiphiles interact strongly. The values of micellar mole fraction (X1) based on the several proposed models (Rubingh, Motomura, and Rodenas) and the ideal micellar mole fraction (Xid) were assessed, and the predicted outcomes indicate that NOT has a significant contribution to the formation of mixed micelles, which increases as the [C14bmim][Br] mole fraction is increased. The negative values of micellization's Gibbs free energy (ΔGm0) between the examined amphiphiles were an indication of spontaneous mixed micelle formation. Micellar changes in entropy (ΔSm0) and enthalpy (ΔHm0) were also computed and discussed. Using surface tension measurements, surface-active parameters like surface tension at cmc (γcmc), minimum surface area per IL molecule (Amin), maximum surface excess concentration (τmax), effectiveness of surface tension reduction (πcmc), and cmc of mixed system have been estimated. The results showed an improved adsorption and micellization properties of these mixtures which will surely contribute to the tremendous rise of these mixed systems in drug delivery applications. [ABSTRACT FROM AUTHOR]

Background: Intraperitoneal metastasis is one of the major causes of the high mortality rate of ovarian cancer. Bufalin (BU) is an effective component of the traditional Chinese medicine Chansu that exerts antitumor effects, including metastasis inhibition. In our previous studies, we found that BU inhibited the migration and invasion of ovarian cancer cells. However, the application of BU is limited due to its insolubility, toxicity and imprecise targeting. The aim of this study was to use vitamin E succinate (VES)-grafted chitosan oligosaccharide (CSO)/arginine-glycine-aspartic acid peptide (RGD)-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles (VeC/T-RGD MMs) to deliver BU to ovarian cancer cells to inhibit intraperitoneal metastasis. Moreover, the toxicity of BU was reduced by coating it with the mixed micelles to increase its biocompatibility for practical applications. Results: The BU-loaded VeC/T-RGD MMs (BU@MMs) had an average diameter of 161 ± 1.4 nm, a zeta potential of 4.49 ± 1.54 mV and a loading efficiency of 2.54%. The results showed that these micelles inhibited cell proliferation, induced apoptosis, and reduced the migration and invasion of A2780 and SKOV3 cells. Further studies indicated that BU@MMs enhanced the levels of e-cadherin and decreased the expression levels of N-cadherin, vimentin and Snail in vitro. In addition, the mixed micelles effectively enhanced the anticancer effect and inhibited intraperitoneal metastasis in intraperitoneal metastatic models. The BU@MMs exhibited fewer toxic side effects than BU, indicating better biocompatibility and biosafety for in vivo applications. Conclusions: Our studies show that BU@MMs are a potential multifunctional nano-drug delivery system that can effectively inhibit the intraperitoneal metastasis of ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract In this article, the effect of the drug aceclofenac (ACF) on the properties of three mixed micellar systems are studied. The three systems were pluronic L64 + F127 (nonionic-nonionic), pluronic L64 + CTAB (cetyltrimethyl ammonium bromide), (nonionic-cationic) and L64 + SDS (Sodium dodecyl sulphate), (nonionic-anionic) combinations. The physicochemical parameters were characterized by different techniques such as UV visible spectroscopy, FTIR, conductance, DLS, and SEM. The presence of ACF affected the nonionic-ionic mixed micelles more than the nonionic-nonionic group as evidenced by UV spectroscopy. From the DLS measurement, it was observed that ACF enhanced the size of the single micelle of pluronic L64 from 98 to 168 nm. The size of the cationic mixed micelle with ACF displayed 329 nm and the anionic mixed one showed 291 nm suggesting enhanced entrapment efficiency of their mixed micelle compared to the single micelles. The size was also reconfirmed by SEM analysis. From the conductivity measurements of the two nonionic-ionic micellar systems, the counter ion binding constant β, and the thermodynamic parameters ΔG, ΔH, and ΔS were determined. The negative value of ΔG infers spontaneous binding between ACF and ionic mixed micelles. Article highlights Ionic mixed micelles are more effective than nonionic pair. ACF has more spontaneous binding with anionic mixed micelle compared to cationic. The drug entrapment efficiency is better in mixed micelles than in single micelles.

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS. Graphical Abstract [ABSTRACT FROM AUTHOR]

In the cleaning field of the cosmetics industry, amino acid surfactants with low irritation and degradability have attracted more and more attention. However, in the actual application system, the amino acid type surfactant has the application difficulty that is not easy to thicken. In this study, the surface activities and application of the surfactant mixtures containing the cationic surfactant dodecyl tri-methyl ammonium chloride (DTAC) and anionic amino acid surfactant sodium lauroyl glutamate (SLG) (cationic/anionic amino acid surfactant system) were systematically studied, which will provide theoretical guidance for practical applications. First, the surface tension of the cationic/anionic amino acid surfactant system was measured, and the CMC value, interaction parameters, Gibbs free energy and other data were obtained. From this, the behavior characteristics of the adsorption and aggregation of SLG and DTAC in the solution can be judged. Then through dynamic light scattering instrument, rheometer, polarizing microscope, etc., we analyze the phase behavior of the cationic/anionic amino acid surfactant system under different compound ratios and different concentrations, and draw a pseudo-ternary phase diagram. Finally, the influence of the length of the hydrophobic chain of cationic surfactants on the phase behavior of amino acid surfactants was investigated. Experiments have found that the addition of cationic surfactant DTAC can significantly reduce the CMC value of the SLG system, and the CMC changes with the increase of the SLG ratio as follows: first decrease and then increase. The interaction parameters show that DTAC and SLG have a strong interaction. Contrary to the phenomenon of precipitation after the compounding of conventional cationic/anionic surfactants, the compounding of DTAC and SLG increases the solubility, reduces the Krafft point of SLG, and increases the application performance. At the same time, the problem of difficult control of the viscosity of the amino acid surfactant system has also been better solved. DTAC and SLG form a worm-like mixed micelle, which has a higher and controllable viscosity. Finally, it was found that changing the hydrophobic chain length of cationic surfactants has a direct effect on the viscosity of the system. [ABSTRACT FROM AUTHOR]

Binary mixtures of surfactants build a binary mixed micelle in which the ratio of surfactants usually differs from the initial ratio of surfactants in their binary mixture. The thermodynamic stabilization of the binary mixed micellar pseudophase about the hypothetical ideal state (intermolecular interactions between the different particles and the conformational states of the particles are identical to those of monocomponent states) is described by the molar excess Gibbs free energy (gE). The dependence of gE on the molar fraction of surfactant i (xi) from the binary mixed micelle can be described by a symmetric function (symmetry is described to the line parallel to the y-axis and passes through xi = 0.5) or by an asymmetric function. Theoretical analysis (canonical partition function, conformational analysis) examines how the presence of different polar functional groups, some of which are sterically shielded from the steroid skeleton of bile salts (surfactant), affect the symmetry of the function gE of the binary mixed micelle of the cholic acid anion (bile salts) and classic cationic surfactant (hydrophobic tail and polar head). Suppose the steroid skeleton of the bile salt contains non-sterically shielded polar groups (or the temperature is relatively high). In that case, gE is a symmetric function. At the same time, if the steroid skeleton also contains sterically shielded polar groups, then the gE function is asymmetric. [ABSTRACT FROM AUTHOR]

This work aimed to develop water-based formulations for onychomycosis topical treatment using micelles of small pegylated surfactants associated with α-cyclodextrin (αCD) to deliver terbinafine to the nail. Kolliphor® RH40 (RH40) and Gelucire® 48/16 (GEL) single and mixed micelles (RH40:GEL 1:1) were prepared. αCD was added to the surfactants dispersions to form poly(pseudo)rotaxanes (PPR). Formulations were characterized in terms of drug solubilization (3 to 34-fold increase), particle size (9–11 nm) and Z-potential (+0.3 − +1.96 mV), blood compatibility (non-hemolytic), rheological behavior (solid-like viscoelastic properties after 5–10% αCD addition), drug release and interaction with the nail plate. GEL micelles and surfactant-10% αCD PPRs notably hydrated the nail plate. The high viscosity of PPR led to a slower drug release, except for RH40:GEL +10% αCD that surprisingly released terbinafine faster. The RH40:GEL +10% αCD formulation delivered twice more amount of terbinafine to deeper regions of nail plate compared to other formulations. The results evidenced the potential of PPR formed by small pegylated surfactants as a water-based formulation for nail drug delivery.

Docetaxel (DTX) has poor solubility, serious side effects, and multi-drug resistance (MDR) limiting its use in cancer treatment. Hence, the present study aimed to formulate and develop docetaxel mixed micelles (DTX MMs) for breast cancer treatment. DTX MMs were prepared from a mixture of docetaxel, TPGS, and Poloxamer 188 by using the solvent evaporation method. A 32 factorial design was applied to examine the combined effect of two formulation variables, each at 3 levels, and the 9 possible combinations of DTX MMs. The concentration of TPGS (X1) and concentration of Poloxamer 188 (X2) were independent variables. Whereas, particle size (Y1), and % entrapment efficiency (%EE) (Y2) were dependent variables. DTX MMs were evaluated for particle size analysis, TEM, %EE, in vitro drug release, %hemolysis, and stability study. DTX MMs composition (F6) was optimized based on particle size (143.2 nm), zeta potential (-7.5 mV) and %EE (81%). The TEM images showed spherical-shaped MMs. DTX MMs showed moderately higher IC50 value, indicating lower cytotoxicity when compared to plain DTX against MCF-7 cells. Docetaxel's sustained release from MMs decreased its exposure to normal tissue. Studies using IR, DSC, and P-XRD showed no significant incompatibility. DTX MMs would be a potential therapy for chemotherapy against breast cancer

We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D5–D7 were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids—compounds 3 and 4—from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D3, a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D3. Compound 3 showed similar uptake levels but transported about half as much as vitamin D3. These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3’s activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D2–D7 and was also predicted to have unique biological activities.

Three cationic surfactants labeled as APS-8 ((Z)-4-(((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)methyl)-N,N-dimethyl-N-octylbenzenaminium bromide), APS-12 ((E)-4-(((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)methyl)-N-dodecyl-N,N-dimethylbenzenaminiumbromide), and APS-16 ((E)-4-(((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)methyl)-N-dodecyl-N,N-dimethylbenzenaminium bromide) were opportunely synthesized in order to study the effect of the hydrocarbon chain length on the process of micellization in mixed surfactant systems. The critical micelle concentration (CMC) values of binary mixtures containing APS-x (x = 8, 12, 16) and a conventional cationic surfactant (cetyltrimethylammonium bromide, CTAB) were retrieved by using surface tension measurements. The behavior of the mixed systems has been analyzed in the light of Rubingh's regular solution theory. In particular, two parameters describing respectively the interactions at the air/water interface and in the micellar phase were obtained for each system. Results show that micellization and adsorption properties of the mixed systems depend on the hydrophobic chain length and on the interaction of APS-x with CTAB. Furthermore, applying the regular solution theory (RST) to the experimental data allowed obtaining the interaction parameter of the mixed micelles (β) and the air–water interface (βσ). Results indicate an attractive interaction between the micelles and reveal a synergistic effect between the two components of the mixtures both in micelles and at the interface. The activity coefficients and the experimental CMC values in micelles indicate synergism less than as well as at the interface. [ABSTRACT FROM AUTHOR]

Self-organization in mixed compositions based on hexadecyltriphenylphosphonium bromide (TPPB-16) and nonionic surfactant Brij 35 was studied using a complex of physicochemical methods (tensiometry, fluorimetry, dynamic light scattering, spectrophotometry) by varying the molar fraction of cationic surfactant (α1 = 0, 0.3, 0.5, 0.7, and 1.0). The solubilization capacities of the obtained nanosized aggregates toward the model hydrophobic probe Orange OT and the drug indomethacin were calculated. The TPPB-16/Brij 35 systems demonstrate a synergistic effect, manifesting itself in a decrease of the critical micelle concentration. The obtained mixed compositions with molar fractions of 0.5 and 0.7 demonstrate solubilization capacities toward Orange OT and indomethacin comparable to those of cationic amphiphile. The formation of the mixed composition TPPB-16/Brij 35 reduces the toxicity of the system while maintaining high functional activity. [ABSTRACT FROM AUTHOR]

The work deals with the extraction and preconcentration of novocaine using mixed surfactants of nonionic (Triton X-114) and anionic (sodium dodecyl sulfate) types with the photometric registration of an analytical signal. The method is based on the condensation reaction of novocaine with p-dimethylaminobenzaldehyde (pH 2.5–3.5) and the subsequent micellar extraction of the colored analytical form, the Schiff base. For the effective extraction of this form, the parameters of micellar extraction (concentrations of reagents: сNaCl = 0.5–1 М, cTriton X-114 = 2 × 10–3–1 × 10–2 M; conditions: centrifugation time 5 min at 3000 rpm) are optimized. The proposed method makes it possible to determine novocaine in the concentration range 38–4800 ng/mL (RSD ≤ 7%, limit of detection 19 ng/mL), which is several orders of magnitude lower than in the known spectrophotometric versions. The Bouguer–Lambert–Beer law is obeyed in the range 8 × 10–7–4 × 10–5 M. The developed extraction-photometric method was tested in the determination of novocaine in 0.5% ampoule solutions for injection. [ABSTRACT FROM AUTHOR]

The catalytic performance of lipase, an interfacially active enzyme, depends on the reaction medium. Novel reaction media like mixed micelles affect lipase catalysis mostly by stabilizing the lipase structure and increasing the substrate solubilization. Nonionic surfactant addition in ionic micelles formed mixed micelles and increased lipase catalysis by lowering detrimental lipase‐ionic surfactant hydrophobic and electrostatic interactions. Nonionic/nonionic mixed micelles enhanced activity and enantiomeric selectivity of free lipase but reduced those for immobilized lipase. Nonconventional cationic/cationic, anionic/nonionic/ionic liquid, and substrate/nonionic mixed micelles also improved lipase catalysis. Lipase activity was high in bile salt/surfactant mixed micelles but was low in bile salt/phospholipid mixed micelle. Mixed micelles have advantages like improving lipase‐substrate interaction, increasing water nucleophilicity, sometimes greater emulsion stability, and reduced product inhibition. In mixed micelles, increasing the lipase concentration can overcome the problem regarding inaccessibility of insoluble substrates. [ABSTRACT FROM AUTHOR]

In this work, the interaction of ponceau 4R dye (P4R) with triple viz., anionic, nonionic and cationic micellar systems has been studied. The three surfactants employed were nonionic pluronic L-64 (PL-64), anionic sodium dodecyl sulphate (SDS) and cationic cetyl trimethyl ammonium bromide (CTAB). All the three dye - surfactants systems were investigated through UV - visible spectroscopy, conductivity, FT-IR, pH effect and SEM studies. There was short and strong bonding between the dye and all the three types of micelles as observed from FT-IR studies. The conductivity studies displayed greater interaction with CTAB than with SDS. The free energy of micellization, ∆G was observed to be -16.07 kJ mol−1 for P4R+ CTAB and -13.83 kJ mol−1 for P4R + SDS, demonstrating greater spontaneity and stability of the former combination. This can be explained due to strong electrostatic attraction between negatively charged P4R dye and positively charged micelle of CTAB. Overall, the anionic ponceau 4R dye has been successfully incorporated into the nonionic, anionic and cationic micellar systems. This is probably the first report of interaction of a similarly charged dye and surfactant system.

[Display omitted] • The bioavailability of the weakly water-soluble AZI could have been enhanced by the CAPB-STS mixed micelle. • The AZI binding constant values were found maximum of 3.144 at α CAPB 0.1of mixed micelle. • Aqueous solubility of AZI 0.0032 mmol/L were enhanced up to 0.048 mmol/L in the presence of mixed micelles. • At α CAPB 0.1 mixed micelles, the controlled release of AZI in PBS at pH 7.4 was found to be 30.77%. The study highlights the importance of mixed micelles in enhancing the binding and solubilization properties of partially water-soluble medications, using zwitterionic cocoamidopropyl betaine (CAPB) and anionic sodium tetradecyl sulfate surfactants. Surface tension and fluorescence spectroscopy evaluated the critical micelle concentration (CMC) of CAPB-STS mixed micelle. The thermodynamic parameters were assessed using Clint, Rubingh, and Motomura's approach, which showed a synergistic interaction between the CAPB and STS. UV spectroscopy technique was used to evaluate the applicability of mixed micelle to enhance the solubility and binding constant (K b) of antibiotic azithromycin dihydrate (AZI). K b values of AZI were increased from 2.301 to 3.415 and molar solubilization ratio (MSR) values of AZI were increased from 0.228 to 0.801 by decreasing α CAPB from 0.9 to 0.1. The result indicated that zwitterionic CAPB was an electrostatic interaction consisting of both attractive (−CH 2 COO¯ group) and repulsive (−N+ group) interactions with AZI (−NH+ group), causing AZI molecules to reside in the Stern layer. While STS consisted of a negative −SO 4 ¯ head group, it caused increased electrostatic interaction, and AZI penetrated the palisade layer of mixed micelles. At 7.00 mmolL-1 concentration of α CAPB 0.1, the solubility of AZI in water was increased to 2.77 mmol/L from 0.0032 mmol/L. Additionally, after 8 h, the controlled release of AZI in PBS at pH 7.4 was 95.58 % and decreased up to 30.77 % at α CAPB 0.1 mixed micelles. The observation of controlled AZI release from α CAPB 0.9 to 0.1 indicates that AZI molecules were strongly bound to mixed micelles by both hydrophobic and electrostatic interactions. In the end, a mixed micelle of CAPB-STS could serve as a useful drug-solubilizing agent in pharmaceutical applications. [ABSTRACT FROM AUTHOR]