Core Of Micelles Research Articles

Highly Sensitive Electrochemiluminescence Biosensing Method for SARS-CoV-2 N Protein Incorporating the Micelle Probes of Quantum Dots and Dibenzoyl Peroxide Using the Screen-Printed Carbon Electrode Modified with a Carboxyl-Functionalized Graphene.

Obtaining stable electrochemiluminescence (ECL) emissions from a hydrophobic luminophore in aqueous solutions and designing a method without the use of an exogenous coreactant are promising for ECL biosensing. Here, a highly sensitive signal-on ECL immunoassay for the SARS-CoV-2 N protein was developed using micelles as an ECL tag. The micelles were prepared by coencapsulating the luminophore hydrophobic CdSe/ZnS quantum dots and coreactant dibenzoyl peroxide within the hydrophobic core of micelles. The ECL probe was obtained by covalently bonding a SARS-CoV-2 N protein-binding aptamer onto the micelle surface. The construction of the immunosensor was initiated by the immobilization of the anti-SARS-CoV-2 N protein antibody onto the screen-printed carbon electrode (SPCE) with a -COOH-functionalized surface. The surface functionalization of SPCEs was achieved through paste-exfoliated graphene, which was modified with a -COOH group through supramolecular-covalent scaffolds on SPCE. Upon achieving sandwich complexes on the immunosensor, an efficient ECL signal response at -1.4 V versus Ag/AgCl was obtained in phosphate buffer solution. The ECL assay was used for the sensitive determination of SARS-CoV-2 N protein with the linear range from 0.01 to 50 ng mL-1, and the detection limit was 3.0 pg mL-1. The immunosensor showed good reproducibility and stability, and the ECL immunoassay was used to determine the SARS-CoV-2 N protein in serum samples. The proposed approach to obtain micelles is versatile for the preparation of stable ECL luminophores by using hydrophobic materials, and the strategy provides an alternative for ECL bioassays based on the coreactant route.

Engineering the reverse micellar-templated Co(OH)2 nanospheres based Pickering emulsion and unveiling the mechanism of ambiguous phase separation

The present study employs reverse micellar-templated Co(OH)2 nanospheres, in situ hydrophobized with SDS in Pickering emulsion formulations and unlocking the mechanism of ambiguous phase separation at a certain surfactant concentration (4.3 mM). Co(OH)2 is synthesised in the core of reverse micelle: SPAN 80/1-butanol/water/toluene. Novel O/W Pickering emulsions have been developed with the help of positively charged (ς = 4.47 mV) Co(OH)2 (0.05 wt%) and an adequate amount of an anionic surfactant, SDS. An ambiguous phase separation of Pickering emulsion at 4.3 mM SDS is noticed within just 4 hr of standings, whereas, surprisingly stable O/W Pickering emulsions are found above and below these SDS concentrations. Upon addition of 2.6 mM SDS to the aqueous colloidal dispersion of Co(OH)2, the particles converted to amphiphilic one and stabilized the Pickering emulsion. However, these monolayer adsorbed surfactants face a hydrophobic interaction through tail-to-tail mode after adding 4.3 mM SDS to the colloidal dispersion. Consequently, they achieve a nanoplates-like architect and regain the extreme hydrophilic surface from both ends and eventually leads to the ambiguous phase separation through inter-droplet coalescence. The contact angle value altering from 44.9° (for 2.6 mM SDS) to 19.6° (for 4.3 mM SDS) confirms that the surface has changed from being amphiphilic to becoming extremely hydrophilic. Yet, again an increase in SDS (6.06 mM and onwards) suggest that surfactant molecules further adsorbed in either any of the two hydrophilic ends and revolving the particles to its previous amphiphilic state and eventually started to stabilise the emulsion droplets.

Molecular simulation on solubilization of fullerene C60 by C12E6 nonionic surfactants

ABSTRACT Coarse grained simulations were adopted to describe the encapsulation and dispersion of fullerene C 60 by hexaoxyethylene dodecyl ether (C 12 E 6 ) surfactants. The self-organised structures of C 12 E 6 molecules in water were captured and the characteristics of micelles composed of different number of C 12 E 6 molecules were analysed. We found that C 60 molecules alone or in clusters can spontaneously translate into the hydrophobic core of micelles. One monomeric C 60 can explore the hydrocarbon-chain region of the micelles with different sizes, and two different preferential locations of C 60 are observed. The small C 60 clusters can disaggregate after entering the micelle. Larger C 60 clusters can penetrate into the micelle as solid-like nanoparticles, although they are partially disaggregated. When investigating the self-assembly of C 12 E 6 surfactants and C 60 molecules, we found that it is very difficult to disperse C 60 in the micelle monomolecularly. At high molar ratio of C 12 E 6 /C 60 , colloidal nanoC 60 aggregates form with C 12 E 6 surfactants adsorbed on the surface. Our simulations provide an explanation for the different observations in fullerene solubilization in micellar solutions and give a guideline for further solubilization of pristine fullerene or small hydrophobic molecules with surfacant micelles, which is helpful for the design of new micelle-based delivery vehicles.

Coarse-Grained Molecular Dynamics Simulation of Heterogeneous Polysorbate 80 Surfactants and their Interactions with Small Molecules and Proteins.

Polysorbate 80 (PS80) is widely used in pharmaceutical formulations, and its commercial grades exhibit certain levels of structural heterogeneity. The objective of this study was to apply coarse-grained molecular dynamics simulations to better understand the effect of PS80 heterogeneity on micelle self-assembly, the loading of hydrophobic small molecules into the micelle core, and the interactions between PS80 and a protein, bovine serum albumin (BSA). Four representative PS80 variants with different head and tail structures were studied. Our simulations found that PS80 structural heterogeneity could affect blank micelle properties such as solvent-accessible surface area, aggregation number, and micelle aspect ratio. It was also found that hydrophobic small molecules such as ethinyl estradiol preferentially partitioned into the PS80 micelle core and PS80 dioleates formed a more hydrophobic core compared to PS80 monooleates. Furthermore, multiple PS80 molecules could bind to BSA, and PS80 heterogeneity profoundly changed the binding ratio as well as the surfactant-protein contact area.

Laser diagnostics of micellar nanoreactors in ZnSO4/water/AOT/heptane reverse microemulsion system

In the article, for the first time, a method has been developed for remote monitoring of the composition of the reaction medium of micellar nanoreactors and for determining the parameters of nanoparticles during their synthesis using Raman spectroscopy. The sensitivity of spectral characteristics to changes in the size of nanoreactors and the concentration of the nanoparticle precursor in reverse ZnSO4/water/AOT/heptane microemulsions has been experimentally established. It has been shown that the intensity of the band of symmetrical S-O stretching vibrations in the Raman spectrum of the ZnSO4/water/AOT/heptane microemulsion can be used to determine the concentration of ZnSO4 in the micelle cores with the accuracy of 2.4 %. The calibration dependence of the center of mass position of the symmetrical O–H stretching vibrations band of the specified microemulsion on the micelles diameter ensures the determination of the sizes of micellar nanoreactors with an accuracy of 11 %.

Study of the effect of ethanol on the properties of poloxamer 338 solutions by rotational viscometry and spin probe method

The aim. Study the properties of 20 % solutions of poloxamer 338 (P338) in water and mixed solvents water-ethanol using rotational viscometry and the spin probe method at various temperatures. Materials and methods. 20 % m/m solutions of P338 in water and water – ethanol mixtures were the objects of research. The solutions were studied by rotational viscometry at various temperatures; the flow behaviour, lower yield stress (t0) and dynamic or apparent viscosity (η) were determined. Spin probes based on fatty acids, which differ in molecular structure, solubility, and radical localization, were added to the solutions. Electron paramagnetic resonance (EPR) spectra were obtained to determine their type and parameters. Results. Depending on the content, ethanol affects the rheological properties of 20 % solution of P338. The solution was demonstrated to be able to thermally induce sol → gel transition at 32 °C when ethanol content is 5 % m/m. The rheological parameters of the gel at 32 °C and 37 °C exhibit an increase (in comparison to the gel without ethanol), accompanied by a reduction in the packing density of polypropylene oxide (PPO) chains within the cores of P338 micelles. At an ethanol content of 10 % m/m, the gel formation temperature rises to 40 °C. At ethanol content of 15 % m/m and above, 20 % P338 solutions do not form gels at temperatures between 25 °C and 40 °C. The values of rotational correlation times (τ) and the order parameter (S) of fatty acid-based spin probes were observed to decrease with increasing ethanol content up to 30 % m/m; in the case of the ammonium salt of 5‑doxylstearic acid (5-DSA NH4 salt), the anisotropic EPR spectra transform, becoming a superposition of two triplets and subsequently a triplet. P338 solutions retain their ability to undergo thermally induced sol ↔ gel transitions as long as the EPR spectra of this probe exhibit anisotropy at temperatures ranging from 25 °C to 37 °C. As the concentration of ethanol in the solution increases, the solvation of the cores of P338 micelles by the dispersion medium of the solution also increases. Conclusions. It was demonstrated that ethanol, when added to the 20 % P338 solution, results in changes to the rheological properties of this solution. However, at the ethanol content of 5-10 % m/m, the ability of P338 to thermally induce sol → gel transition remains unaltered. The rheological properties of the 20 % P338 solution exhibit a correlation with the observed change in EPR spectra types for the 5-DSA NH4 salt. As the ethanol content in the solution increases, the solvation of P338 micelle cores by the dispersion medium increases, accompanied by decreased density and orderliness of the PPO chains packing in the micelle cores

Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers.

To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

Umbrella‐Shaped Amphiphiles: Internal Alkylation of an Aromatic Micelle and Its Impact on Cavity Features

AbstractTo develop new hybrid micelles with alkyl/polyaromatic core–shell structures, we synthesized umbrella‐shaped amphiphiles bearing a bent anthracene dimer with a linear alkyl chain (i.e., octyl and hexadecyl groups). The amphiphiles quantitatively assemble into spherical micelles (~2–3 nm in core diameter), possessing an alkylated cavity surrounded by a polyaromatic framework, in water. The alkylation significantly enhances the stability of the micellar structures against dilution (up to 9 μM) and heat (up to >120 °C). The highly condensed hexadecyl core of the hybrid micelle, as indicated by solvatochromic guest probes, displays increased uptake ability toward large alkylated metallodyes. Interestingly, efficient uptake of aromatic macrocycles (i.e., [n]cycloparaphenylenes) by the present micelle provides pseudorotaxane‐shaped host–guest composites with high emissivity (ΦF=up to 35 %). Internal multi‐alkylation of an aromatic micelle can thus successfully enhance its assembly stability/guest uptake functions.

Umbrella-Shaped Amphiphiles: Internal Alkylation of an Aromatic Micelle and Its Impact on Cavity Features.

To develop new hybrid micelles with alkyl/polyaromatic core-shell structures, we synthesized umbrella-shaped amphiphiles bearing a bent anthracene dimer with a linear alkyl chain (i.e., octyl and hexadecyl groups). The amphiphiles quantitatively assemble into spherical micelles (~2-3 nm in core diameter), possessing an alkylated cavity surrounded by a polyaromatic framework, in water. The alkylation significantly enhances the stability of the micellar structures against dilution (up to 9 μM) and heat (up to >120 °C). The highly condensed hexadecyl core of the hybrid micelle, as indicated by solvatochromic guest probes, displays increased uptake ability toward large alkylated metallodyes. Interestingly, efficient uptake of aromatic macrocycles (i.e., [n]cycloparaphenylenes) by the present micelle provides pseudorotaxane-shaped host-guest composites with high emissivity (ΦF=up to 35 %). Internal multi-alkylation of an aromatic micelle can thus successfully enhance its assembly stability/guest uptake functions.

RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CURCUMIN AND RESVERATROL IN NANO-MICELLE: DUAL DRUG DUAL FORM SIMULTANEOUS ESTIMATION

Objective: To develop a reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous estimation of conjugated form of Curcumin (CCMN) and free form of Resveratrol (RSV) in nano-micelle. Methods: The conjugation of lipophilic CCMN and hydrophilic Chitosan (CHT) through succinyl linker produce amphipathic molecule that can self-assemble into RSV solution to form micelle. Here RSV exists in micelle core as free form and CCMN with micelle backbone as conjugated form. So it required to estimate conjugated drug and free drug simultaneously from nano-micelle. We developed a RP-HPLC method, utilized C18 column, follow flow rate of mobile phase 1.0 ml/min, which consist of acetonitrile with water (0.5% Ortho Phosphoric acid, pH 4.6) in the ratio of 1:1 for 20 min. Injection volume was 10μl and column temperature 25 ℃. Isosbestic detection of both drugs was at 254 nm. Results: The retention time of RSV and CCMN were at 8.15 min and 11.41 min respectively, completely distinguished sharp peak of CCMN and RSV developed with resolution 7.360±0.117, wide range of linearity with correlation coefficient value (R2) of CCMN and RSV were 0.99987 and 0.99992 respectively and recovery value of CCMN and RSV were 100.041±0.22 % and 100.041±0.21 % respectively. The RSD (relative standard deviation) for accuracy, precision and robustness of the method was found to be less than 2%. Conclusion: The develop method for simultaneous estimation of conjugated CCMN and free form of RSV in the nano-micelle formulation was consider to be accurate, precise, robust and sensitive.

Impact of binary inorganic salt on micellization of pluronic block copolymers: A photophysical analysis

The impact of binary inorganic salt zinc chloride (ZnCl2) on the micellization behavior of triblock pluronic copolymer, F108 was investigated by various spectroscopic methods in the presence of Coumarin-6 (C6) as a fluorescent probe. Ground and excited state photophysical properties revealed that the microenvironment around the C6 molecule changes in the presence of ZnCl2 compared to that in a salt-free solution. The addition of salt to the medium increases the hydrophobicity and microviscosity of the micelle core. Due to the presence of ZnCl2, the central PPO core experiences dehydration, reduces the interaction between water molecules and PEO groups, and enhances the hydrophobic interaction between C6 and hydrophobic PPO parts in the micelle with more solubility of C6. This study helps to develop the property of copolymers as drug carriers in various pharmaceutical applications and drug delivery systems.

Amino-Functionalized Pluronic F127 micelles as a dual drug delivery nanostructure for controlled therapeutics release

Bacterial infection is one of the serious leading causes of hospitalization. The development of a novel dual drug delivery nanostructure based on polymeric micelles is presented here for the treatment of Staphylococcus aureus-associated infections. The nanostructure was composed of quercetin (QC)-encapsulated in the core of F127 micelles (FQ micelles) which was later shell cross-linked using 3-amisinopropyl triethoxysilane (APTES) molecules through condensation reaction. The functionalization of the head groups of FQ micelles with APTES (FQA NPs) facilitated the covalent linkage of vancomycin (Vanc) drug and consequent formation of FQA-Vanc NPs with the hydrodynamic size of 133 nm. FQA-Vanc NPs demonstrated prolong release of QC and Vanc over a period of 168 h. The core–shell structure offered sustainable release of Vanc and QC to the FQA-Vanc NPs during 96 h and 48 h, respectively. The co-administration of Vanc and QC not only enhanced the antibacterial performance of FQA-Vanc NPs, but also induced time and concentration-dependent antioxidant activities. Overall, the Vanc immobilized-FQA NPs together with antibacterial and antioxidant activities could potentially provide a new therapeutic platform for bacterial infection treatment.

Specific FRET Probes Sensitive to Chitosan-Based Polymeric Micelles Formation, Drug-Loading, and Fine Structural Features.

Förster resonance energy transfer (FRET) probes are a promising tool for studying numerous biochemical processes. In this paper, we show the application of the FRET phenomenon to observe the micelle formation from surfactants, micelles self-assembling from chitosan grafted with fatty acid (oleic-OA, or lipoic-LA), cross-linking of SH groups in the micelle's core, and inclusion and release of the model drug cargo from the micelles. Using the carbodiimide approach, amphiphilic chitosan-based polymers with (1) SH groups, (2) crosslinked with S-S between polymer chains, and (3) without SH and S-S groups were synthesized, followed by characterization by FTIR and NMR spectroscopy. Two pairs of fluorophores were investigated: 4-methylumbelliferon-trimethylammoniocinnamate-rhodamine (MUTMAC-R6G) and fluorescein isothiocyanate-rhodamine (FITC-R6G). While FITC-R6G has been described before as an FRET-producing pair, for MUTMAC-R6G, this has not been described. R6G, in addition to being an acceptor fluorophore, also serves as a model cytostatic drug in drug-release experiments. As one could expect, in aqueous solution, FRET effect was poor, but when exposed to the micelles, both MUTMAC-R6G and FITC-R6G yielded a pronounced FRET effect. Most likely, the formation of micelles is accompanied by the forced convergence of fluorophores in the hydrophobic micelle core by a donor-to-acceptor distance (r) significantly closer than in the aqueous buffer solution, which was reflected in the increase in the FRET efficiency (E). Therefore, r(E) could be used as analytical signal of the micelle formation, including critical micelle concentration (CMC) and critical pre-micelle concentration (CPMC), yielding values in good agreement with the literature for similar systems. We found that the r-function provides analytically valuable information about the nature and mechanism of micelle formation. S-S crosslinking between polymer chains makes the micelle more compact and stable in the normal physiological conditions, but loosens in the glutathione-rich tumor microenvironment, which is considered as an efficient approach in targeted drug delivery. Indeed, we found that R6G, as a model cytostatic agent, is released from micelles with initial rate of 5%/h in a normal tissue microenvironment, but in a tumor microenvironment model (10 mM glutathione), the release of R6G from S-S stitched polymeric micelles increased up to 24%/h. Drug-loading capacity differed substantially: from 75-80% for nonstitched polymeric micelles to ~90% for S-S stitched micelles. Therefore, appropriate FRET probes can provide comprehensive information about the micellar system, thus helping to fine-tune the drug delivery system.

Polydopamine coated surfactin micelles for brain delivery of ibudilast in multiple sclerosis: Design, optimization, in vitro and in vivo evaluation

Ibudilast inhibits TNF-α and IL-12 release from the astrocytes and microglial cells, reducing neuronal degeneration and may be a potential therapy in multiple sclerosis with neuroprotective effects. Our study aimed to prepare polydopamine coated micelles of surfactin, a biosurfactant, loaded with ibudilast to control the release and its targeted delivery through nose to the brain by targeting D2-like dopamine receptors limited in olfactory nerve of the bulb. Micelles were prepared by solvent evaporation and film hydration method and optimized to quantify the effects of excipients on particle size and entrapment efficiency. Polydopamine coating on the surface of surfactin micelles was characterized by studying the physicochemical properties of the micelles. Drug concentration in brain after 14 days of administration of the oral, and nasal free drug and also 3 doses of intranasal PDA coated micelles of ibudilast were determined by reverse-phase HPLC method. FTIR results confirmed successful coating of PDA on surfactin micelles and DSC and XRD results indicated solubilization of ibudilast in the core of micelles in an amorphous state. The morphology of the micelles by TEM showed spherical structures with coating of PDA on the shell of the micelles. Particle size of the micelles was 131.3 ± 12.6 nm, zeta potential 27.3 ± 1.7 mV, ibudilast loading percent was 90.2 ± 1.6% and drug release efficiency percent was 72.3 ± 6.5% in the best formulation for surfactin micelles. However, after PDA coating the particle size changed to 174.6 ± 15.7 nm, zeta potential varied to −41.0 ± 2.7 mV, PDA content was 70.3 ± 5.2%, and drug release efficiency percent was 52.9 ± 2.9%. Ibudilast brain concentration was significantly (p < 0.05) higher in PDA coated micelles than oral or nasal free drug.

Teaching an Old Dog New Tricks: A Global Approach to Enhancing the Cytotoxicity of Drug-Loaded, Non-responsive Micelles Using Oligoelectrolytes.

Polymeric micelles have been extensively studied as vectors for the delivery of hydrophobic drugs for the treatment of cancers and other diseases. Despite intensive research, few formulations provide significant benefits, and even fewer have been clinically approved. While many traditional non-responsive micelles have excellent safety profiles, they lack the ability to respond to the intracellular environment and release their cargo in a spatiotemporally defined manner to effectively deliver large doses of cytotoxic drugs into the cytosol of cells that overwhelm efflux pumps. As a novel and adaptable strategy, we hypothesized that well-established non-responsive polymeric micelles could be augmented with a pH-trigger via the co-encapsulation of cytocompatible oligoelectrolytes, which would allow rapid cargo release in the endosome, leading to increased cytotoxicity. Herein, we demonstrate how this strategy can be applied to render non-responsive micelles pH-responsive, resulting in abrupt cargo release at specific and tunable pH values compatible with endosomal delivery, which significantly increased their cytotoxicity up to 3-fold in an ovarian adenocarcinoma (SKOV-3) cell line compared to non-responsive micelles. In comparison, the oligoelectrolyte-loaded micelles were significantly less toxic to healthy 3T3 fibroblasts, indicating a selective cargo release in cancer cell lines. Oligoelectrolytes can be co-encapsulated in the micelles along with drugs at high encapsulation efficiency percentages, which are both ejected from the micelle core upon oligoelectrolyte ionization. Mechanistically, the increase in cytotoxicity appears to also result from the accelerated endosomal escape of the cargo caused by disruption of the endosomal membrane by the simultaneous release of the oligoelectrolytes from the micelles. Furthermore, we show how this approach is broadly applicable to non-responsive micelles regardless of their composition and various classes of hydrophobic chemotherapeutics. The preliminary studies presented here reveal the versatility and wide scope of oligoelectrolyte-mediated, pH-triggered drug release as a compelling and powerful strategy to enhance the cytotoxicity of non-responsive polymeric micelles.

Ionic Strength-Dependent Structure of Complex Coacervate Core Micelles.

Salt concentration-dependent structure of complex coacervate core micelles (C3Ms), formed by polyether-based block copolyelectrolytes containing cationic ammonium (A) or anionic sulfonate (S) groups in aqueous media, is investigated by light scattering and small-angle X-ray/neutron scattering (SAX/NS). As the salt concentration increases, both a core radius (Rcore) and an aggregation number (Nagg) significantly decrease, but a corona thickness (Lcorona) is nearly unchanged. Larger salt concentrations can lower the interfacial tension between the coacervate cores and aqueous media, resulting in an increased interfacial area per chain and a more relaxed conformation of the core blocks. Based on the structure characterization, the scaling relationship between structure parameters (i.e., Rcore, Nagg, and Lcorona) and salt concentration is obtained and compared to the theoretical description estimated by the free energy balance between the entropic penalty of core stretching and the interfacial energy. We propose that the free energy contribution of the core block stretching is not negligible in C3Ms because of the highly swollen cores caused by water.

Assessing the Structure and Equilibrium Conditions of Complex Coacervate Core Micelles by Varying Their Shell Composition and Medium Ionic Strength.

Complex coacervates result from an associative phase separation commonly involving oppositely charged polyelectrolytes. When this associative interaction occurs between charged-neutral diblock copolymers and oppositely charged homopolymers, a nanometric aggregate called a complex coacervate core micelle, C3M, is formed. Recent studies have addressed the issue of their thermodynamic or kinetic stability but without a clear consensus. To further investigate this issue, we have studied C3Ms formed by the combination of poly(diallyldimethylammonium) and copolymer poly(acrylamide)-b-poly(acrylate) using different preparation protocols. Dynamic light scattering and small-angle X-ray scattering measurements suggest that these structures are in an equilibrium condition because the aggregates do not vary with different preparation protocols or upon aging. In addition, their stability and structures are critically dependent on several parameters such as the density of neutral blocks in their shell and the ionic strength of the medium. Decreasing the amount of copolymer in the system and, hence, the density of neutral blocks in the shell results in an increase in the aggregate size because of the core growth, although their globular shape is retained. On the other hand, larger clusters of micelles were formed at higher ionic strengths. Partially replacing 77% of the copolymer with a homopolymer of the same charge or increasing the ionic strength of the system (above 100 mmol L-1 NaCl) leads to a metastable state, after which phase separation is eventually observed. SAXS analyses reveal that this phase separation above a certain salt concentration occurs due to the coagulation of individual micelles that seem to retain their individual globular structures. Overall, these results confirm earlier claims that equilibrium C3Ms are achieved close to 1:1 charge stoichiometry but also reveal that these conditions may vary at different shell densities or higher ionic strengths, which constitute vital information for envisioning future applications of C3Ms.

An Adjuvant Micelle-Based Multifunctional Nanosystem for Tumor Immunotherapy by Remodeling Three Types of Immunosuppressive Cells.

Immunotherapy is restricted by a complex tumor immunosuppressive microenvironment (TIM) and low drug delivery efficiency. Herein, a multifunctional adjuvant micelle nanosystem (PPD/MPC) integrated with broken barriers and re-education of three classes of immune-tolerant cells is constructed for cancer immunotherapy. The nanosystem significantly conquers the penetration barrier via the weakly acidic tumor microenvironment-responsive size reduction and charge reversal strategy. The detached core micelle MPC could effectively be internalized by tumor-associated macrophages (TAMs), tumor-infiltrating dendritic cells (TIDCs), and myeloid-derived suppressor cells (MDSCs) via mannose-mediated targeting endocytosis and electrostatic adsorption pathways, promoting the re-education of immunosuppressive cells for allowing them to reverse from pro-tumor to antitumor phenotypes by activating TLR4/9 pathways. This process in turn leads to the remodeling of TIM. In vitro and in vivo studies collectively indicate that the adjuvant micelle-based nanosystem not only relieves the intricate immune tolerance and remodels TIM via reprogramming the three types of immunosuppressive cells and regulating the secretion of relevant cytokines/immunity factors but also strengthens immune response and evokes immune memory, consequently suppressing the tumor growth and metastasis.

A deeper insight into the evaluation of water-in-oil amicroemulsion templated samarium sulfide nanospheres: exploring its role in pickering emulsion formulation for photocatalytic dye degradation and synthesis of PANI@Sm2S3 nanocomposites.

This study examines the effectiveness of W/O microemulsion-mediated Sm2S3 nanospheres in pickering emulsion-based crystal violet (CV) dye degradation and PANI@Sm2S3 nanocomposite synthesis. The evaluation of nanospheres inside the core of reverse micelles was performed through DLS, TEM and FESEM analyses. The formation of nanospheres involve two phases: a nucleation phase (5-30 min) and growth phase (30-120 min). Through in situ hydrophobization of negatively charged (with a zeta value of -4.47 mV at neutral pH) Sm2S3 nanoparticles (0.1 wt%) with a suitable amount of a cationic CTAB surfactant, a stable O/W pickering emulsion was developed. 0.1 wt% Sm2S3in situ hydrophobized with 2.7 mM CTAB offered a stable pickering emulsion with a diameter of 23 μm after 1 day of storage. This pickering emulsion improves the local concentration of CV by efficiently encapsulating dye molecules inside the core of emulsion droplets. Therefore, dye molecules get numerous opportunities to interact with the Sm2S3 photocatalyst and efficiently degrade. The pickering emulsion stabilised by 0.1 wt% of Sm2S3 nanoparticles in situ hydrophobized with 2.7 mM of CTAB results in almost 100% degradation. Moreover, using only solid Sm2S3 (having wt% of 0.025 or 0.075) as a pickering stabiliser, new PANI@Sm2S3 spherical nanocomposites were synthesised via pickering emulsion polymerization. The formation of PANI@Sm2S3 composites was identified via UV-vis, IR, and 1H-NMR investigations. The analysis of FESEM images showed that the amount of nanoparticles used in the dispersion (for 0.025 wt%, 35 nm and 0.075 wt%, 29 nm) strongly influences the size and shape of the composites.

Thermal stability of water-in-oil microemulsions containing solubilized nutritional protein gelatin

To develop new food and pharma technologies, various combinations of encapsulation and delivery of biological macromolecules are used. Proteins, polysaccharides, fats and lipids must be conveyed inside living organism, protecting them during the stages of storage and preparation from exposure of aggressive external environment. Some of the most common food protein compositions are various gels and emulsions. In the present study, we focused our attention on the influence of protein molecules on the properties and dynamical stability of water-inoil microemulsion. Microemulsions, the oil dispersion of surfactant-based reverse micelles, each carrying nanosized water core with embedded protein. We studied the result of protein encapsulation in the water core of surfactant reverse micelles, namely, the fish and mammalian gelatin. The method of electric conductivity was explored to detect the properties of reverse micelles as containers for food proteins. We have shown that a rather high protein content does not destroy microemulsion structure, which retain reverse micelles, though the properties of the system undergo definite alterations, in particular, it substantively lost thermal stability accelerating exchange processes between reverse micelles at lower temperatures which have to be taken into account in nutritional and pharmacy objectives.