Single Micelle Research Articles

Ultrasmall single micelle@resin core-shell nanocarriers as efficient cargo loading vehicles for in vivo biomedical applications.

Ultrasmall core-shell nanocarriers (NCs) are believed to be ideal candidates for biological applications, as proved by silica-based core-shell NCs fabricated using a single micelle as a template. Compared with inert silica, polymers with various properties play an essential and ubiquitous role in our daily life. However, the fabrication of polymer-based NCs with ultrasmall particle size (less than 20 nm) is still very limited, which is probably hindered due to the difficulty in handling the polymeric process and the soft nature of most polymers. In this study, we demonstrated the fabrication of ultrasmall single micelle@resin core-shell NCs through a single micelle template method using resorcinol-formaldehyde resins (RFRs) as model polymers. Moreover, the fluorescence properties of the ultrasmall single micelle@resin core-shell NCs could be adjusted from visible light to near-infrared through the incorporation of different dye molecules. The fluorescent single micelle@RFR core-shell NCs show extra-low cytotoxicity and great potential in both in vitro and in vivo bioimaging and photothermal therapy applications.

A tadpole-shaped gene carrier with distinct phase segregation in a ternary polymeric micelle.

A distinct tadpole-shaped nanostructure characterized by a spherical head and an extended shaft was identified in a single plasmid DNA (pDNA)-based polymeric micelle. The tadpole-shaped structure was constructed by adding anionic chondroitin sulfate (CS) to the rod-shaped polyplex micelle containing a single pDNA molecule packaged by the PEG-polycation block copolymer through their electrostatic self-assembly. The complex consequently developed a novel structure composed of segregated domains of the CS-rich inflated head and CS-poor folded DNA tail. Hence, this tadpole structure can be regarded as evidence that distinct phase segregation occurred in a single polymeric micelle containing pDNA.

Customizing wormlike mesoscale structures via self-assembly of amphiphilic star polymers.

We examine the phase behavior of end-functionalized diblock copolymer stars by means of Grand Canonical Monte Carlo simulations. We focus on solutions of diblock copolymer stars with a solvophobic outer block shorter than the solvophilic inner block, which are expected to nucleate microphase aggregates. By tuning the temperature and rigidity of the molecules, we target specific mesoscale structures, which can act as powerful rheology modifiers. In particular, we control the hierarchical self-assembly of single micelles in a "pearl-necklace" fashion, which eventually merge into elongated, wormlike supermicelles.

Electrochemical detection of single micelles through 'nano-impacts'.

A new class of 'soft' particles, micelles, is detected electrochemically via 'nano-impacts' for the first time. Short, sharp bursts of current are used to indicate the electrical contact of a single CTAB (cetyltrimethylammonium bromide) micelle with an electrode via the oxidation of the bromide content. The variation in CTAB concentration for such 'nano-impact' experiments shows that a significant number of 'spikes' are observed above the CMC (critical micelle concentration) and this is attributed to the formation of micelles. A comparison with dynamic light scattering is also reported.

Azide-functionalized hollow silica nanospheres for removal of antibiotics

Antibiotics, which are hardly removed from polluted water by conventional water-treatment technologies, adsorption has been deemed as one of the efficient and promising method to resolve the problems of antibiotics pollution. Herein, we reported a synthesis of filtration separable hollow nanostructured silicas (HNSs) with efficient click functionalization property for antibiotics adsorption. The clickable HNSs were synthesized by the co-condensation and assembling of tetramethoxysilane (TMOS) and 3-azidopropyltrimethoxysilane (AzPTMS) around F127 single micelle template. Alkynyl compounds such as phenylacetylene (Ph), propargyl alcohol (PA), 1-heptyne (Hep), and 2-butyne-1,4-diol (BD) have been linked to the materials through click reaction with high efficiency. Antibiotic adsorption results reveal that functional groups play an important role in adsorption properties of adsorbents and phenyl was found to be the optimal functional group due to the π–π stacking effect. Excellent adsorption capacity and recyclability indicate that the clickable hollow nanostructured silicas exhibit potential application for antibiotics removal.

Monitoring Micelle Formation of Nonionic Polyurethane in Water by Fluorescence Spectrophotometry

A series of nonionic polyurethanes were dissolved in water and their miceller self-assembly behaviors were characterized by aid of a fluorescence spectrophotometer. Fluorescence and resonance light scattering techniques were carried out for characterizing the micelles, and information such as aggregation number, critical micelle concentration, micropolarity, and micelle volume change was obtained. The micropolarity decreased as the aggregation number increased. The nonionic polyurethane micelle volume with two long ethoxyl chains per polyurethane molecule was smaller than the one with short chains, even with the same aggregation number, and was less polar. The micropolarity depended on both the aggregation number and the volume of a single micelle.

Molecular dynamic simulations of self-assembly of amphiphilic comb-like anionic polybenzoxazines.

Fully atomistic molecular dynamic simulations were performed to address the self-assembly of amphiphilic and comb-like polybenzoxazines (iBnXz) in water, with i = 3 (trimer), i = 4 (tetramer); i = 6 (hexamer), i = 8 (octamer), and i = 10 (decamer). Spontaneous aggregation of these comb-like polybenzoxazine molecules into a single micelle occurs in the simulations. The simulations show that molecular size and concentration play important roles in micellar morphology. At an iBnXz concentration of 50 mM, the 3BnXz and 4BnXz molecules aggregate into spherical micelles, whereas the 6BnXz, 8BnXz, and 10BnXz molecules aggregate into cylindrical micelles. The micellar morphology is spherical at low concentrations, but undergoes a transition to cylindrical shape as concentration increases. The transition point depends on the molecular size-both the true size as indicated by molecular weight, as well as an additional effective size dependent on molecular flexibility.

Isothermal titration calorimetric analysis on solubilization of an octane oil-in-water emulsion in surfactant micelles and surfactant–anionic polymer complexes

Polymers may alter the ability of surfactant micelles to solubilize hydrophobic molecules depending on surfactant–polymer interactions. In this study, isothermal titration calorimetry (ITC) was used to investigate the solubilization thermodynamics of an octane oil-in-water emulsion in anionic sodium dodecylsulphate (SDS), nonionic polyoxyethylene sorbitan monooleate (Tween 80), cationic cetyltrimethylammonium bromide (CTAB) surfactant micelles and respective complexes formed by these micelles and an anionic polymer (carboxymethyl cellulose). Results indicated that the oil solubilization in single ionic micelles was endothermic, while in nonionic micelles or mixed ionic/nonionic micelles it was exothermic. The addition of carboxymethyl cellulose did not influence the solubilization behavior in these micelles, but affected the solubilization capacities of these systems. The solubilization capacity of cationic micelles or mixed cationic/nonionic micelles was enhanced while that of nonionic or anionic micelles was decreased. Based on the phase separation model, a molecular pathway mechanism driven by enthalpy was proposed for octane solubilization in surfactant micelles and surfactant–polymer complexes.

ChemInform Abstract: Polymeric Micelles as Drug Delivery Vehicles

AbstractReview: 119 refs.

Surfactant–surfactant and surfactant–solute interactions in SLES–Brij35 mixed micelles: Effect of the degree of ethoxylation on pyrene solubilization enhancement in water

We investigated the effect of the degree of ethoxylation on surfactant–surfactant (βM) and surfactant–solute (B) interactions toward pyrene solubilization in water using sodium lauryl ether sulfate (SLES) containing 1–3 OE groups per molecule and Brij35 mixed micelles. In single SLES micelles, pyrene MSR (and Km) increased with increasing degree of ethoxylation, but remained invariant in SLES–Brij35 mixed micelles at any given Brij35 molar fraction composition in the bulk (α). Upon increasing α, a direct correlation between the variation of the CMCs and MSRs was observed, suggesting that the negative deviation of the CMCs from ideal mixing behavior and the increase in Km12 are two influencing factors in pyrene solubilization in mixed micelles. The increase in Km12 was attributed to the opening up of mixed micelle from a random coil structure to a more stretched one with the increase in Brij35 molar fraction. The invariance of CMCs, MSRs, and Km12 with SLES degree of ethoxylation (at fixed α) was reflected by similar invariance in βavgM (−2.01) and X1M, suggesting identical mixed micelle structure and aggregation properties. On the other hand, although Km12 values were independent on the degree of ethoxylation at fixed composition α, B decreased with increasing degree of ethoxylation. This was considered as an evidence that pyrene–SLES interaction plays an insignificant role in the positive synergism observed in this study, compared to SLES–Brij35 interaction.

Physiological pH-triggered morphological transition of amphiphilic block copolymer self-assembly

In order to develop polymeric self-assembly with an intelligent morphological transition property under appropriate stimuli, a series of pH-sensitive amphiphilic block copolymers have been prepared via atom transfer radical polymerization (ATRP). Due to the delicately designed macromolecular structure, poly(ethylene glycol)44-b-poly(2-diisopropylaminoethyl methacrylate)15 (PEG44-b-PDPA15) could form self-assemblies with a controllable morphological transition in response to the physiological pH changes. As demonstrated by the results of dynamic light scattering (DLS) records and transmission electron microscopy (TEM) micrographs, PEG44-b-PDPA15 could self-assemble into toruloid aggregates arranged by several single micelles at pH 7.4, but the morphology changed into uniform single micelles at pH 6.5. With a further decrease of pH value to 5.5, PEG-b-PDPA became double hydrophilic and could not self-assemble into any nanostructure. Therefore, this block copolymer provides a feasible approach to construct a nanoscale smart self-assembly with adjustable morphologies, which exhibits its potential for biomedical applications with specific physiological pH stimuli, such as intracellular delivery and tumor therapy.

Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable production of reactive oxygen species

Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and β-carotene (CAR) as a singlet oxygen (1O2) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated 1O2 through direct 1O2 scavenging, whereas the CAR molecules lost their 1O2 scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a 1O2 generator and a 1O2 scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment.

A dual-targeting nanocarrier based on modified chitosan micelles for tumor imaging and therapy

Conventional chemotherapy suffers from non-specificity, lack of aqueous solubility and multidrug resistance. Tumor-targeting nanotherapeutics exhibit unique advantages in the delivery of drugs specifically into tumors. Here, folic acid (FA), methionine (Met) and a near infrared (NIR) fluorescence probe (cypate, ICG derivative) were all bio-conjugated to succinyl-chitosan (SC) micelles. An anti-cancer drug (paclitaxel, PTX) was loaded into the hydrophobic cores of the formed FA–Met–SC–ICG derivative (FMSCI) micelles, which were under 200 nm in size. In comparison with micelles containing a single targeting moiety (FA or Met), FA and Met co-mediated micelles presented excellent biocompatibility, much higher affinity for cancer cells and excellent tumor-specific distribution in tumor-bearing mice. In vivo anti-tumor activity demonstrated that PTX-loaded FMSCI provided favourable therapeutic efficacy for tumors. In this research, novel nanotherapeutics based on FMSCI loaded with an anti-cancer drug provide a promising nanocomposite for combined tumor-targeting imaging and therapy.

Enhancing fluorescence by using pluronic block copolymers as carriers of monomeric porphycenes

Porphycenes, structural isomers of porphyrins, usually exhibit strong fluorescence in organic solvents. However, in water they are practically insoluble or form only weakly emitting aggregates. We show that embedding porphycenes inside pluronic micelles in water solutions leads to the recovery of strong monomeric fluorescence, of which the decay times and quantum yields are similar to those observed for homogeneous solvents. One of the investigated porphycenes serves as a fluorescence sensor of the microenvironment viscosity, revealing that the viscosity inside pluronic micelles is quite high. Using confocal fluorescence microscopy, we obtained images of single pluronic micelles containing monomeric porphycene chromophores.

PH-responsive stealth micelles composed of cholesterol-modified PLA as a nano-carrier for controlled drug release.

Present research is a preliminary report on the novel pH-responsive micelles based on an amphiphilic brush copolymer P(PEGMA)-b-P(DMAEMA-co-CPLAMA) used as the promising drug carrier. The copolymer was synthesized using cholesteryl poly(l-lactic acid) methacrylate (CPLAMA), poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) with appropriate hydrophobic/hydrophilic ratios via atom transfer radical polymerization. The copolymer compositions were determined by 1H NMR. The synthesized copolymer self-assembled into nano-scale micelles capable of encapsulating hydrophobic model drug naproxen in their hydrophobic cores in aqueous solutions. pH sensitivity and self-assembly behaviors of copolymer were studied by UV–vis transmittance, fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The results showed that the copolymer had high pH responsivity with a phase transition pH around pH 6.2. The critical micelle concentrations at pH 6.5 were found about 2.4 mg L−1. The stable and small micelles were obtained at pH 5.5–6.5. Upon increasing pH higher than 7, the single micelles further assembled into the micellar aggregates. TEM images of copolymer micelles showed that the micelles are spherical in shape with the mean diameter of 152 nm at pH 6.2. In vitro release study of naproxen-loaded micelles with about 44 % loading efficiency and 8 % loading capacity was performed using dialysis method in phosphate-buffered solution at 37 °C. Release study implied that the proposed brush copolymer could produce stable nano-carriers with controllable drug release at the target sites (pH 5.5–7).

Polypeptide‐Based “Smart” Micelles for Dual‐Drug Delivery: A Combination Study of Experiments and Simulations

A dual-drug-loaded micelle is designed and constructed from a mixture of poly(propylene oxide)-b-poly(γ-benzyl-l-glutamate)-b-poly(ethylene glycol) (PPO-b-PBLG-b-PEG) triblock terpolymers and two model drugs, doxorubicin (DOX) and naproxen (Nap). In the micelles, the DOX is chemically linked to the PBLG backbones through an acid-cleavable hydrazone bond, whereas the Nap is physically encapsulated in the cores. The drug loading and releasing behaviors of the dual-drug-loaded micelles as well as single drug-loaded micelles (DOX-conjugated or Nap-loaded micelles) are studied. The structures of micelles are characterized by means of microscopies and dynamic light scattering, and further examined by dissipative particle dynamics (DPD) simulations. It is revealed that the micelles possess a core-shell-corona structure in which the PPO/Nap, PBLG/DOX, and PEG aggregate to form the core, shell, and corona, respectively. In vitro studies reveal that the release of DOX and Nap is pH- and thermosensitive. Such drug releasing behaviors are also examined by DPD simulations, and more information regarding the mechanism is obtained. In addition, the bio-related properties such as cellular uptake of the micelles and biocompatibility of the deliveries are evaluated. The results show that the dual-drug-loaded micelles are biocompatible at normal physiological conditions and retain the anti-cancer efficiency.

Competitive solubilization of low-molecular-weight polycyclic aromatic hydrocarbons mixtures in single and binary surfactant micelles

Abstract The present study aims to assess mutual interaction among low-molecular-weight polycyclic aromatic hydrocarbons (LMW PAHs), predominant contaminants at petroleum contaminated sites, in nonionic, anionic and their mixed micelles. Cosolubilization effects were evaluated by the molar solubilization ratio, the micelle-water partition coefficient and the deviation ratio. Two conditions existed: (i) naphthalene/phenanthrene and naphthalene/fluorene, with significant different hydrophobicities, showed synergistic effect, a new finding compared to previous observations that no more than one solute’s solubility would increase when two solubilizates coexisted, e.g. solubility of naphthalene and phenanthrene in Triton X-100 was increased by 20.8% and 38.5% when cosolubilized, respectively and (ii) phenanthrene/fluorene, with similar hydrophobicity, exhibited inhibitive effect due to competition for the same solubilization sites, i.e. solubility of phenanthrene and fluorene in Triton X-100 was decreased by 36.1% and 6.5% when cosolubilized, respectively. Solubility of PAHs with higher log K ow gained larger enhancement. Synergism was stronger in bisolutes solubilization system where more PAHs could solubilize in the micellar shell region. Solubility inhibition was more intense to PAHs with lower log K ow . The cosolubilization trends were consistent in single and mixed surfactant systems, whereas the enhancing and suppressive extent, on the whole, were weakened and strengthened with increasing mole ratio of anionic surfactant in the mixed micelles because of reduction in micelle size. This study suggested the significance of considering multi-solutes’ interaction to estimate solubilization power of surfactants for selective separation of LMW PAHs from water and soil.

Micellar self-assemblies of gadolinium(iii)/europium(iii) amphiphilic complexes as model contrast agents for bimodal imaging

The synthesis and characterization of two novel DTPA bisamide derivatives DTPA-BC12PheA and DTPA-BC14PheA functionalized with p-dodecylaniline and p-tetradecylaniline are described. The ligands were coordinated to Gd(iii) and Eu(iii), resulting in highly paramagnetic and luminescent complexes, respectively. Mixed micelles consisting of Gd/Eu-DTPA-BC12PheA and DTPA-BC14PheA with a homogeneous size distribution (33-40 nm) were prepared by the assembly of the amphiphilic complexes with phospholipid DPPC and a surfactant Tween 80®. Taking into account the sensitivity difference between magnetic resonance and optical imaging techniques, the ratios of Gd and Eu complexes (Gd/Eu) 1 : 1, 2 : 1, 3 : 1, 20 : 1 and 50 : 1 were combined in one single micelle and their optical and relaxometric properties were characterized in detail. Upon excitation at 290 nm, the micelles display characteristic red emission bands due to the (5)D0→(7)FJ (J = 0-4) transitions of Eu(iii). The number of water molecules in the first coordination sphere of Eu(iii) (qEu = 0.1-0.2) was calculated from the lifetime measurements performed in H2O and D2O solutions. Micelles composed of exclusively europium complexes display quantum yields in the range of 1.0%, decreasing with the europium concentration when going from 1 : 1 to 50 : 1 Gd/Eu contents. The ligand-to-lanthanide sensitization efficiency for micelles consisting of Eu-DTPA-BC12PheA and Eu-DTPA-BC14PheA equals 3.8% and 4.1%, respectively. The relaxivity r1 per Gd(iii) ion at 40 MHz and 310 K reaches a maximum value of 14.2 s(-1) mM(-1) for the Gd-DTPA-BC12PheA assemblies and 16.0 s(-1) mM(-1) for the micellar Gd-DTPA-BC14PheA assemblies compared to a value of 3.5 s(-1) mM(-1) for Gd-DTPA (Magnevist®). Theoretical fitting of the (1)H NMRD profiles results in τR values of 4.2 to 6.6 ns. The optimal concentration ratio of Gd/Eu compounds in the micelles in order to provide the required bimodal performance has been determined to be 20 : 1. In the search for other bimodal systems, this discovery can be used as a guideline concerning the load of paramagnetic agents with respect to luminescent probes.

Self-assembling Behaviors of Symmetric Diblock Copolymers in C Homopolymers

The micelle formation of AB symmetric diblock copolymers in C homopolymers (or solvents) is studied by means of the calculations of the self-consistent field theory. Under the condition that C homopolymer has no preferential interaction for any of the two blocks, anisotropic ellipsoidal micelles, which are composed of segmented layers of A/B do- mains with a normal direction along the major axis of ellipsoid, are observed. The length ratio, the ratio of the major axis of an ellipsoidal micelle to its minor axis, is used to quantify the extent of anisotropy. We systematically study the formation of a single micelle in our calculations, through focusing on the length ratio as functions of the volume of micelles, the A/B in- teractions as well as the length of homopolymer, instead of considering a huge system consisting of a number of micelles with variable volumes. Our results are presented through three main conclusions. First, with fixed interactions, the length ratio of micelles decreases as increasing the micellar volume. When the micellar volume is raised to some critical extent, one more layer of A or B domains is added into the micelle, which leads to a sudden jump of the major axis, thereby inducing a corresponding increase of the length ratio. Second, for a given micellar stucture with fixed volume, the length ratio of micelle continuously rises up as adding the incompatibility of the two blocks. While the incompatibility rises up to high enough, the length ratio varies more mildly because the energy arising from the packing frustation has overwhelmed the interfacial energy between block copolymers and homopolymers. Third, for a micelle with fixed interaction and volume, the length ratio in- creases as reducing the length of homopolymer. In a limit case of small molecule solvent, the length ratio goes up to an ex- tremely large value, thereby forming a worm-like micelle. Our results are of great interest for the understanding of the re- sponse of the micelles with segmented layers of A/B domains to enviromental conditions, including temperature (imcompati- bility), homopolymer (or solvent), and shearing (volume). Keywords block copolymer; self-assembly; self-consistent field theory; micelle; the length ratio

The Solubilization Capability of Polycyclic Aromatic Hydrocarbons Enhanced by Biosurfactant Saponin Mixed With Conventional Chemical Surfactants

Water solubilities of anthracene and phenanthrene were measured by adding a plant-derived biosurfactant Saponin and/or synthetic surfactants correspondingly below and above their critical micelle concentrations (CMCs). The results showed that the solubilities of anthracene and phenanthrene in water were greatly enhanced following a linear fashion if adding Saponin, TX100 and Brij35, respectively. The enhancing solubility capacities for Polycyclic aromatic hydrocarbons (PAHs) followed the order as: Saponin > Brij35 > TX100 at the concentrations below their CMC. It also proved that biosurfactant Saponin exhibited much higher enhancement efficiency for PAHs solubilization than the synthetic ones at the concentrations below the CMC. However, the solubility enhancement efficiencies of surfactants above the CMC turned to be the following order as Brij35 > Saponin > TX100. Furthermore, this study has confirmed that PAHs are synergistically solubilized in the mixed biologic-synthetic surfactant solutions, especially at the low surfactant concentrations.Synergistic effect of a prepared mixed-surfactant solution on different PAH compounds also appeared to be linear related to the surfactant concentrations. The synergistic power of mixed surfactants were examined as Saponin-Brij35 > Saponin-TX100 while the efficiencies of synergistic solubilization ranged from 27% to 137%. The noted solubilization for the single and mixed surfactants could be attributed to the formation of single and mixed micelles, the lower CMC of the single and mixed surfactant solutions, and the increase of the solubilization ratio or micellar partition coefficients.