Spherical Mixed Micelles Research Articles

Development of docetaxel-loaded (Soluplus®–PF108) mixed micelles vacuum foam-dried product for improved stability and melanoma treatment by QbD approach

BackgroundDocetaxel (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.ResultsThe 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.ConclusionThis 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

Regular solution theory for nonlinear composition dependency of enantioselectivity by mixed micelle

Mixtures of chiral and achiral building blocks of supramolecules exhibit interesting cooperative properties, as indicated by the nonlinear relationship between chiral properties and the mole fraction of chiral building blocks. However, the nonlinear composition dependence of the chiral recognition capability of spherical mixed micelles is poorly understood. This study hypothesized that the phenomenon could be described by the regular solution theory reported to be able to describe critical micelle concentration (CMC) and partition coefficients of the mixed micelle by interaction parameters β and B, respectively. The CMC and mole fraction of chiral surfactant in the mixed micelle were simulated by using the theory of varying β and CMC of the two surfactants. Equations that describe the enantioselectivity are newly derived in this work, and the dependency of the enantioselectivity on B was studied in detail. The regular solution theory was applied to the mixed micellar electrokinetic chromatography (MEKC) for the first time. It was found that the formula can describe the nonlinear composition dependency of the enantioselectivity of the mixed MEKC. The partition coefficient determined by MEKC was in agreement with the β versus B relation, which was previously reported.

SDS triggered transformation of highly hydrophobic Pluronics® nanoaggregate into polymer-rich and surfactant-rich mixed micelles

This work reveals the role of sodium dodecylsulphate (SDS, anionic surfactant) in altering the phase behaviour and aggregation characteristics of five very hydrophobic polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymers containing 10% PEO but with different molecular weight. These copolymers are molecularly dissolved in water at ≤15–20 °C and exist as unstable vesicular structure at temperature close to cloud point (CP) >20 °C. SDS enhanced the aqueous solubility and CP of copolymers in water; progressive addition of SDS triggered the transformation of unstable vesicles into spherical mixed micelles. A correlation between the molecular orbital energy levels of Pluronics® and SDS is well comprehended using computational simulation approach where the perception of SDS stabilized Pluronics® micelles is predicted and correlated with optimized parameters. The size/ shape of copolymer-surfactant mixed nanoscale aggregates was evaluated using dynamic light scattering (DLS) and small-angle neutron scattering (SANS). The scattering studies showed the presence of spherical mixed aggregates, whose size expanded with increase in hydrophobicity of Pluronics®. In high SDS concentration regime, SANS analysis uncovered the diminishing size of vesicles into spherical mixed aggregates. The nanoscale Pluronics®-SDS mixed micelles remained stable in water where this investigation discloses the conceivable ability of orange-OT solubilization using UV–vis spectroscopy.

Shape and Structure Formation of Mixed Nonionic-Anionic Surfactant Micelles.

Aqueous solutions of a nonionic surfactant (either Tween20 or BrijL23) and an anionic surfactant (sodium dodecyl sulfate, SDS) are investigated, using small-angle neutron scattering (SANS). SANS spectra are analysed by using a core-shell model to describe the form factor of self-assembled surfactant micelles; the intermicellar interactions are modelled by using a hard-sphere Percus–Yevick (HS-PY) or a rescaled mean spherical approximation (RMSA) structure factor. Choosing these specific nonionic surfactants allows for comparison of the effect of branched (Tween20) and linear (BrijL23) surfactant headgroups, both constituted of poly-ethylene oxide (PEO) groups. The nonionic–anionic surfactant mixtures are studied at various concentrations up to highly concentrated samples ( ≲ 0.45) and various mixing ratios, from pure nonionic to pure anionic surfactant solutions. The scattering data reveal the formation of mixed micelles already at concentrations below the critical micelle concentration of SDS. At higher volume fractions, excluded volume effects dominate the intermicellar structuring, even for charged micelles. In consequence, at high volume fractions, the intermicellar structuring is the same for charged and uncharged micelles. At all mixing ratios, almost spherical mixed micelles form. This offers the opportunity to create a system of colloidal particles with a variable surface charge. This excludes only roughly equimolar mixing ratios (X≈ 0.4–0.6) at which the micelles significantly increase in size and ellipticity due to specific sulfate–EO interactions.

Rebaudioside A/TPGS mixed nanomicelles as promising nanocarriers for nimodipine ocular delivery.

Nimodipine (NMD), a calcium channel blocker, has demonstrated benefits in treating glaucoma. However, its ocular therapeutic application remains limited due to its poor aqueous solubility, which restrains the development of an ophthalmic formulation. Thus, the present study aimed to formulate an NMD micelle ophthalmic solution to enhance the potential of NMD in an ocular topical formulation to treat glaucoma. The NMD micelle ophthalmic solution was formulated with nanocarriers composed of rebaudioside A and D-α-tocopheryl polyethylene glycol 1000 succinate. Spherical mixed micelles were optimized and obtained at a small micelle size 13.429 ± 0.181nm with a narrow size distribution (polydispersity index 0.166 ± 0.023) and high encapsulation efficiency rate (99.59 ± 0.09%). Compared with free NMD, NMD in micelles had much greater in vitro membrane permeability and antioxidant activity. The NMD micelle ophthalmic solution was well tolerated in rabbit eyes. It profoundly improved the in vivo intraocular permeation of NMD, and in vivo intraocular pressure reduction and improved miosis were also observed. Accordingly, this NMD micelle ophthalmic solution might be a promising ocular formulation to treat glaucoma. Graphical abstract.

Nanostructured hybrid fluids of amphiphilic diblock copolymers and surfactant worm-like micelles complexes

This paper reports the synthesis and characterization of two poly(methyl methacrylate)-block-poly(2-(dimethylamino)ethyl methacrylate) diblock copolymers and their synergistic interaction with cetyltrimethylammonium tosylate (CTAT) worm-like micelles (WLMs) in aqueous solutions. The rheological behavior of the mixtures of the copolymers and CTAT was compared with the water soluble homopolymer, poly(2-(dimethylamino)ethyl methacrylate). The polymers were synthesized via ATRP, and were characterized using GPC, FTIR and 1H NMR. The rheological behavior of CTAT WLMs was explored under continuous shear flow, varying the (co)polymer concentration, adding salt to the (co)polymer/CTAT systems and changing the pH and the temperature. The effect of the copolymer on CTAT pseudoplasticity reveals the synergy between both compounds, leading to mixed worm like micelles. Based on our rheological results, spherical mixed micelles are not formed for the systems studied since shear induced structures (SIS) were formed even at high (co)polymer concentration. These SIS are characteristic of CTAT worm-like micelles and demonstrate that the surfactant keeps its micellar configuration in water, albeit modified by the co-micellization with the (co)polymer molecules. We demonstrate that shear produces a more pronounced effect in the viscosity of CTAT/polymer mixed worm-like micelles for systems containing interacting diblock copolymers than those containing homopolymers. The novel copolymer/surfactant fluids prepared here exhibit viscosities that can be tuned from 10 to 10,000 times the viscosity of water by selecting molecular weights, solution concentrations, ionic environment, temperature and shear rates.

Nanostructural Evolution and Self-Healing Mechanism of Micellar Hydrogels

Understanding the nanoscale structure and dynamics of supramolecular hydrogels is essential for exploiting their self-healing mechanisms. We describe here nanostructural evolution and self-healing mechanism of hydrogels formed from in situ generated hydrophobically modified hydrophilic polymers and wormlike sodium dodecyl sulfate (SDS) micelles. We observe a conformational transition in wormlike SDS micelles upon addition of hydrophobic as well as hydrophilic monomers. Several hundred nanometer long SDS micelles completely disappear after the monomer addition, in favor of spherical micelles with a radius of 2.4 nm. After conversion of the monomers to hydrophobically modified polymer chains via micellar copolymerization, the spherical shape of the micelles remains intact but the radius increases to 2.8 nm. The interconnected spherical mixed micelles consisting of SDS and hydrophobic blocks of the polymer self-assemble to form a layered hydrogel structure. Self-healing response of the damaged hydrogel sampl...

Investigations on microstructural changes in pH responsive mixed micelles of Triton X-100 and bile salt

Aqueous solution behaviour of a nonionic surfactant Triton X-100 is investigated in the presence of two bile salts namely sodium deoxycholate (NaDC) and sodium cholate (NaC) at different pH, temperatures and in the presence of sodium chloride and the resultant structural changes to accordingly formed mixed micelles were analyzed by using cloud point (CP), viscosity and scattering techniques. Both the bile salts increased the CP and showed a corresponding decrease in viscosity and apparent hydrodynamic diameter (Dh), which can further be subsided with the progressive addition of sodium chloride and an increase in temperature. Interestingly, in the presence of bile salt below pH ∼5, CP decreased with corresponding increase in viscosity, while a reversed trend was observed above pH∼8. Small angle neutron scattering data reveal that nearly spherical mixed micelles were formed in the presence of bile salt which grow and transform to prolate ellipsoidal ones at pH∼3. These morphological changes are facilitated by the protonation of carboxylic acid group of bile salt and deeper penetration of bile acid molecules into TX-100 micelles at lower pH. Proposed molecular interactions are extremely informative to understand more about these biologically important compounds playing a crucial role in digestion processes.

Influence of Headgroup on the Aggregation and Interactional Behavior of Twin-Tailed Cationic Surfactants with Pluronics

The surface tension measurements have been employed to characterize the micellar and interfacial behavior of pure and mixed systems of twin-tailed cationic surfactants: dimethylene bis(decyldimethylammonium bromide) (10-2-10), didecydimethylammonium bromide (DDAB), and 1,3-didecyl-2-methylimidazolium chloride (DDIC) with pluronics P84 and F108 in the aqueous solution. The interactions of each surfactant with both pluronics are found to be nonideal and synergistic except for the mixed system of 10-2-10 + F108, for which interactions are antagonistic and every interaction has been studied on the basis of headgroup disparity. Dynamic light scattering (DLS), zeta (ζ) potential, and small angle neutron scattering (SANS) measurements have been used to determine the influence of the mixing ratio on the morphology of the various mixed aggregates that are formed. Pure DDAB is found to form unilamellar vesicles whereas pure 10-2-10 and DDIC form prolate ellipsoidal micelles. The unilamellar vesicles of DDAB are destructed to yield spherical mixed micelles on addition of pluronics via expansion or contraction of vesicles. However, the pure pluronics and their mixed systems with 10-2-10 and DDIC form charged spherical micelles, and charge is confirmed by thenfractional charge and ζ values. The ζ values of pure surfactants are found to decrease on addition of pluronics, indicating a decrease in surface charge on inclusion of pluronics.

Structural transition in aqueous lipid/bile salt [DPPC/NaDC] supramolecular aggregates: SANS and DLS study

Small angle neutron scattering (SANS) and dynamic light scattering (DLS) were used to study different aggregation states in sodium deoxycholate (NaDC)-phosphatidylcholine systems at T=60°C. Size and shape of the aggregates investigated as a function of the NaDC bile salt concentration (at the constant DPPC concentration of 6mM) indicate a strong dependence of the size and morphology of the generated aggregates on the relative amount of NaDC bile salt. More specifically large occupied area of the bile salt induces a steric interaction which promotes the transition toward a variety of supramolecular structures ranging from ellipsoidal vesicles, ribbon-like structures, up to final spherical mixed micelles at the large amount of bile salt of 10mM NaDC. The findings of the obtained results give important insight for understanding the formation of different topologies in aqueous lipid–bile salt mixtures as well as stimulate new routes for liposome reconstitution–solubilisation processes suitable for technological applications.

A Calorimetry and Light Scattering Study of the Formation and Shape Transition of Mixed Micelles of EO20PO68EO20Triblock Copolymer (P123) and Nonionic Surfactant (C12EO6)

The interaction between the nonionic surfactant C12EO6 and the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer EO20PO68EO20 (P123) has been investigated by means of isothermal titration and differential scanning calorimetry (DSC) as well as static and dynamic light scattering (SLS and DLS). P123 self-assembles in water into spherical micelles at ambient temperatures. At raised temperatures, the DSC data revealed a sphere-to-rod transition of the P123 micelles around 60 degrees C. C12EO6 interacts strongly with P123 micelles in aqueous solution to give mixed micelles with a critical micelle concentration (cmc) well below the cmc for pure C12EO6. The presence of C12EO6 also lowers the critical micelle temperature of P123 so aggregation starts at significantly lower temperatures. A new phenomenon was observed in the P123-C12EO6 system, namely, a well-defined sphere-to-rod transition of the mixed micelles. A visual phase study of mixtures containing 1.00 wt % P123 showed that in a narrow concentration range of C12EO6 both the sphere-to-rod transition and the liquid-liquid phase separation temperature are strongly depressed compared to the pure P123-water system. The hydrodynamic radius of spherical mixed micelles at a C12EO6/P123 molar ratio of 2.2 was estimated from DLS to be 9.1 nm, whereas it is 24.1 nm for the rodlike micelles. Furthermore, the hydrodynamic length of the rods at a molar ratio of 2.2 is in the range of 100 nm. The retarded kinetics of the shape transition was detected in titration calorimetric experiments at 40 degrees C and further studied by using time-resolved DLS and SLS. The rate of growth, which was slow (>2000 s), was found to increase with the total concentration.

Formation of mixed micelles of PB40PEO62and the anionic surfactant SDS in aqueous solutions

Co-micellisation of the di-block copolymer polybutadiene-poly(ethylene oxide) (B40-b-EO62) with the anionic surfactant sodium dodecylsulfate (SDS) was investigated in aqueous solution using different scattering methods and cryo-transmission electron microscopy. In dilute aqueous solutions this polymer forms large wormlike micelles coexisting with spherical ones. Upon addition of the surfactant, the large, mainly wormlike block copolymer micelles exhibit a structural change. Mixed micelles of polymer and surfactant are formed and the size of the mixed aggregates changes in dependence on the amount of SDS. At a certain limiting concentration of SDS, only spherical mixed micelles with a radius of ca. 13 nm and a low polydispersity are observed in the solution. Further addition of surfactant does not induce any further structural change.

Structural changes of poly(butadiene)-poly(ethyleneoxide) diblock-copolymer micelles induced by a cationic surfactant: scattering and cryogenic transmission electron microscopy studies.

Micelles of the diblock copolymer poly(butadiene)-poly(ethyleneoxide) (B40-b-EO62) and mixed micelles of this polymer with the cationic surfactant dodecyltrimethylammonium bromide (C12TAB) were investigated using static and dynamic light scattering and small-angle neutron scattering. It is shown that the surfactant induces a major structural change from large mainly rodlike aggregates to smaller spherical mixed micelles. The rodlike assemblies found in the absence of surfactant have a contour length L of ca. 500 nm and a diameter d approximately 30 nm. The spherical mixed micelles obtained upon addition of C12TAB possess a hydrodynamic radius of 15 nm and still contain several polymer molecules. The results of the scattering experiments are consistent with observations of the aggregates by cryogenic transmission electron microscopy.

Self-Assembly in the System Decanoic Acid–Butylamine–Water

The phase behavior of alkanoic acid–alkylamine mixtures in water is mainly dictated by a proton transfer from the acid to the amine. For an asymmetric distribution of carbon atoms in the alkyl chains, the result will be an ionic surfactant with an organic counter-ion. In this study the phase diagram at 298.2 K for the ternary system decanoic acid–butylamine–water has been determined. The phase diagram is dominated by a large isotropic solution region. The self-diffusion, viscosity, and conductivity measurements in the solution phase for an equimolecular ratio between the acid and the amine indicate a continuous transition from aqueous spherical mixed micelles to highly interacting hydrated acid–amine complexes passing through a bicontinuous region. One liquid crystalline lamellar phase, existing at excess acid, has been found. The small angle X-ray scattering results indicate that the amine, due to its slightly amphiphilic character, is distributed between water and the bilayer.

Electrical structure of ((dodecyloxy)methyl)-18-crown-6 micelles in aqueous potassium chloride solutions: electrophoretic light scattering and 2D NMR

The ζ-potential of spherical mixed micelles of ((dodecyloxy)methyl)-18-crown-6 in 0.1 mol/dm 3 KCl varies with temperature, having a minimum near 25°C, though the hydrodynamic radius of the micelles is approximately constant below 35°C