Micelles In Terms Research Articles

Enhanced thermodynamic, pharmacokinetic and theranostic properties of polymeric micelles via hydrophobic core-clustering of superparamagnetic iron oxide nanoparticles

BackgroundSuperparamagnetic iron oxide nanoparticles (SPIO) have been applied for decades to design theranostic polymeric micelles for targeted cancer therapy and diagnostic MR imaging. However, the effects of SPIO on the physicochemical, and biological properties of polymeric micelles have not yet been fully elucidated. Therefore, we investigated potential effect of SPIO on the physical and biological properties of theranostic polymeric micelles using representative cancer drug (doxorubicin; Doxo) and polymer carrier (i.e., poly (ethylene glycol)-co-poly(D,L-lactide), PEG-PLA).MethodsSPIO were synthesized from Fe(acetyl acetonate)3 in an aryl ether. SPIO and Doxo were loaded into the polymeric micelles by a solvent-evaporation method. We observed the effect of SPIO-clustering on drug loading, micelle size, thermodynamic stability, and theranostic property of PEG-PLA polymeric micelles. In addition, cellular uptake behaviors, pharmacokinetic and biodistribution study were performed.ResultsSPIO formed hydrophobic geometric cavity in the micelle core and significantly affected the integrity of micelles in terms of micelle size, Doxo loading, critical micelle concentration (CMC) and in vitro dissociation. In vivo pharmacokinetic studies also showed the enhanced Area Under Curve (AUC) and elongated the half-life of Doxo.ConclusionsClustered SPIO in micelles largely affects not only MR imaging properties but also biological and physical properties of polymeric micelles.

INTERACTION OF 3-HYDROXY PYRIDINE AND SURFACTANT MICELLES: A FLUORESCENCE STUDIES

Objective: Micellar solubilization is a powerful alternative for dissolving hydrophobic compound in aqueous environment. 3-hydroxy pyridine (3- HP) derivatives are the potential endogenous photosensitizers. 3-HP derivatives show protective effect in clinical extreme condition such as hypoxia, hyperthermia, hypokinesia. Micellization of 3-HP followed by solubilization would catalyze its pharmaceutical activities which may serve better results in medicinal and analytical fields. Methods: Fluorescence and absorption spectroscopy techniques are used to monitor the micellar solubilization studies of 3-HP. Solubilization studies of 3-HP with various anionic, cationic and nonionic surfactants have been performed in aqueous medium around 23–25°C temperature. The solubilization action of the surfactant has also been determined by theoretical calculated spectral parameters such as empirical fluorescence coefficient, quantum yield, stokes, shift and molar absorption coefficient. Results: 3-HP shows fluorescence excitation peak at 315 nm and emission peak at 390 nm respectively while the absorbance of 3-HP has been found to be maximum at 305 nm. The fluorescence as well as the theoretically calculated spectral data has been used to characterize the hetero environment of the micelles in terms of their polarity, probe solubilization site and critical micelle concentration. Conclusion: This article briefly discusses the importance of surfactants in biological system model as well as the use of micelles in pharmacy as an important tool that finds numerous applications.

Characterization of charged polymer self-assemblies by multidetector thermal field-flow fractionation in aqueous mobile phases

Charged block copolymer self-assemblies, such as charged micelles, have attracted much attention as versatile drug delivery systems due to their readily tunable characteristics such as size and surface charge. However, current column-based analytical techniques are not suitable to fractionate and comprehensively characterize charged micelles in terms of size, molar mass, chemical composition and morphology. Multidetector thermal field-flow fractionation (ThFFF) is shown to be a unique characterization platform that can be used to characterize charged micelles in terms of size, molar mass, chemical composition and morphology in aqueous mobile phases with various ionic strengths and pH. This is demonstrated by the characterization of poly(methacrylic acid)-b-poly(methyl methacrylate) self-assemblies in high pH buffers as well as the characterization of cationic poly(2-vinyl pyridine)-b-polystyrene and poly(4-vinyl pyridine)-b-polystyrene self-assemblies in low pH buffers. Moreover, it is shown that ThFFF is capable of separating charged micelles according to the corona composition. These investigations prove convincingly that ThFFF is broadly applicable to the comprehensive characterization of amphiphilic self-assemblies even when aqueous mobile phases are used.

Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10–100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer–polymer and polymer–cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

Apparent voluminosity of casein micelles in the temperature range 35–70 °C

Casein micelles are basic units of dairy matrices that can be aggregated by reducing their electrostatic repulsion or by surface modifications. Studying casein micelles in terms of a colloidal suspension demands of a preferably complete physico-chemical characterisation. Process control in dairy technology as well as mechanistic models that explain the formation and structure of dairy products build on the specific hydration of the casein micelles. The effect of the temperature on the voluminosity of native casein micelles at pH 6.6–6.7 was investigated using rheometry covering a wide range of temperatures and mass fractions. Increasing temperature resulted in a constant decrease of the voluminosity up to 70 °C. A quadratic polynomial was tested to fit the temperature dependency the best. The apparent voluminosity of casein micelle suspensions was determined with 4.0 mL g−1 at 35 °C, 3.6 mL g−1 at 50 °C, and 3.5 mL g−1 at 70 °C.

Tumor-binding prodrug micelles of polymer–drug conjugates for anticancer therapy in HeLa cells

An interesting phytosphingosine (PHS), a natural sphingolipid metabolite comprising ceramides, is believed to play a vital role in strong anticancer therapeutic efficacy for various types of cancer cells, which is based on a programmed cellular death mechanism, so called apoptosis. However, extremely low water-solubility has been an obstacle to its usage as an anticancer drug via the systemic administration route. To utilize the benefits of PHS, we developed tumor-targeting polymer–drug conjugates wherein hydrophobic PHS was connected to the folate-grafted hydrophilic and biocompatible polymer through pH-sensitive linkages. The polymer–drug conjugates formed nano-sized (10–20 nm) spherical micelles spontaneously in aqueous media and they were found to have high drug contents (10.3 wt%). We present a systematic study of in vitro anticancer therapy in HeLa cells treated by tumor-targeting micelles in terms of anti-proliferation. The anticancer effect was analyzed by apoptotic cell death as well as the preferential distribution of loaded drug in the cancer cells. The synergistic effect by loading the commercial drug of doxorubicin was also studied.

Structure of Nonionic Surfactant (Glycerol α-Monomyristate) Micelles in Organic Solvents: A SAXS Study

In this paper we present the study of reverse micellar aggregates formed by glycerol alpha-monomyristate (C(14)G(1)) in different organic solvents. We have investigated the structure (mainly shape and size) of the monomyristin reverse micelles depending on alkyl chain length of the oils, temperature, and the surfactant concentration. Moreover, we present how addition of trace polar additives such as water or glycerol and the hydrophilic size of the surfactant affect the structure of the micelles. Monomyristin could not form any self-organized structure in nonpolar media at room temperature because of its smaller headgroup size and tends to separate from the nonpolar media. In dilute regions this surfactant forms a solid dispersion, which upon heating transforms into an isotropic reverse micellar solution. For the structural characterization of the reverse micelles formed at elevated temperatures, we have performed small-angle X-ray scattering (SAXS) measurements, and the data were analyzed utilizing the generalized indirect Fourier transformation (GIFT) method. The SAXS data have shown that the size of the reverse micelles increases with the alkyl chain length of oils and surfactant concentration but decreases with temperature. A dramatic growth to the micelles could be achieved when the hydrophilic size of the surfactant is increased. Furthermore, addition of trace water or glycerol induces a significant change in the structure of micelles in terms of a cross-section and maximum length. The added water tends to form a water pool in the micellar core and results in swollen micelles. Model-free cross-section analysis of the SAXS data provided complementary information on the structural parameters. Thus, the present study has highlighted the possible ways of controlling the structure, mainly the shape and the size of the inverse micelles.

PH- and temperature-dependent phase behavior of a PEO-PPO-PEO-based pentablock copolymer in aqueous media

We investigated the structural features of micelles formed by the self-association of the pentablock copolymer poly[ N,N -(diethyl amino)ethyl methacrylate]-block-poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethyleneoxide)-block-poly[ N,N -(diethylamino)ethyl methacrylate] (PDEAEM-PEO-PPO-PEO-PDEAEM) in aqueous solutions by using small-angle neutron scattering SANS. The pentablock copolymer solutions exhibit micellar and gel phases in response to changes in both the temperature and pH by virtue of (1) the lower critical solution temperature of the PPO blocks and (2) the polyelectrolyte character of the pendant PDEAEM blocks. Two modeling schemes were employed to describe the SANS data of semidilute copolymer solutions at higher temperature as they contain interacting charged micelles at pH<7.5 and interacting neutral micelles at higher pH. We have elucidated the structures of the micelles in terms of size, shape, polydispersity, association number, number density, and surface charge. At low pH the charged spherical micelles are less packed with the copolymers presumably due to the electrostatic repulsion between the charged pendant groups. On the other hand, at higher pH the hydrophobic character of the neutral pendant groups enable them to sequester within the micelle core along with the PPO, thus increasing the number density and the core size of the spherical micelles. At higher copolymer concentration reversible thermoresponsive sol-gel transitions were observed at all pH conditions and the rheological behavior of the gels nicely correlates with different organization of micelles with different shapes.

Micelles in Anticancer Drug Delivery

In recent years, the development of micelle-based carriers for cancer chemotherapy has been the object of growing scientific interest, both in academia and the pharmaceutical industry. Micelles have attracted attention in drug formulation and targeting, given that they provide a set of unique features. The core/shell structure accounts for their qualities as efficient drug delivery systems. The core provides a reservoir where hydrophobic drugs can be dissolved, and the corona confers hydrophilicity to the overall system. Sequestration of anticancer drugs in the inner core can protect them from premature degradation and allow their accumulation at tumoral sites. Micelles can be subdivided into two different groups according to their molecular weights: low-molecular-weight surfactant micelles and polymeric micelles. Although surfactant micelles such as polyethoxylated castor oil (e.g. Cremophor® EL) are commonly used to solubilize hydrophobic anticancer drugs such as paclitaxel, they have often been associated with serious adverse effects. Polymeric micelles may offer several advantages over surfactant micelles in terms of drug loading, adverse effects, stability, and targeting of tumors. Indeed, polymeric micelles can increase the circulation time of cytostatics and induce substantial changes in their biodistribution, including tumor accumulation via the enhanced permeation and retention effect. In addition, some recent studies have demonstrated that amphiphilic block copolymers (e.g. poloxamers) used for the preparation of polymeric micelles could increase the activity of several cytostatics by reversing multidrug resistance. This review first describes and compares surfactant micelle and polymeric micelle systems, already commercialized or under investigation, used to administer cytostatics. Secondly, their in vitro interactions with neoplastic cells and tissues are discussed in terms of cellular uptake and pharmacologic activity. In particular, the pharmacokinetics and biodistribution of micelles, along with the factors affecting their delivery to tumoral sites, are thoroughly discussed. Finally, in vivo studies reporting the anticancer activity and toxicity of drugs associated with micelles are reviewed.

Effect of microheterogeneous media on the fluorescence and fluorescence probe properties of donor–acceptor diarylbutadienes

Diarylbutadienes, namely 1-(para-cyanophenyl)-4-phenylbuta-1E,3E-diene (1), 1-(para-methoxyphenyl)-4-phenylbuta-1E,3E-diene (2), 1-(para-cyanophenyl)-4-(para-methoxyphenyl)-buta-1E,3E-diene (3) have been prepared and investigated for their absorption and fluorescence properties in homogeneous media of organic solvents, dioxane–water binary mixtures and in the microheterogeneous media of sodium dodecyl sulfate, cetyl trimethyl ammonium bromide and Triton-X-100 micelles. The fluorescence behaviour in various media has been correlated in terms of empirical solvent parameters such as Dimroth ET(30) and Kamlet–Taft π* values, and Kirkwood functions. A Linear correlation between solvent polarity and fluorescence properties is observed. In ethanol–methanol (1:1, v/v) matrix at 77 K, a blue-shifted fluorescence maximum with enhanced fluorescence quantum yields is observed for dienes 2 and 3. The singlet excited state of diene 3 is found to be highly polar in nature. The fluorescence peak intensity of dienes 1 and 2 and the fluorescence emission wavelength maximum (λf max) of diene 3 undergo significant changes upon changing the concentration of surfactants. The fluorescence properties of these dienes have been further used to characterize the micelles in terms of their critical micelle concentration and micropolarity.

Interaction of tryptophan and N-acetyltryptophanamide with dodecylpentaoxyethyleneglycol ether micelles

Through the fluorimetric determination of the critical micellar concentration of dodecylpentaoxyethyleneglycol ether and sodium dodecylsulfate, we have investigated the interaction of the zwitterionic tryptophan and its uncharged analogue N-acetyl- l-tryptophanamide with micelles in terms of binding constants. This could be useful to monitor protein interaction with different membrane-like environments using the intrinsic tryptophan fluorescence. The weakest interaction took place between tryptophan and sodium dodecylsulfate, while the strongest one occurred between N-acetyl- l-tryptophanamide and dodecylpentaoxyethyleneglycol ether. This suggests that micelle head groups control the interaction, but the polar moiety bringing the fluorophore also seems to play a role. The unexpected lack of interaction between tryptophan and dodecylpentaoxyethyleneglycol ether is also discussed.

Structure and rheology of wormlike micelles

The analysis of wormlike micelles in terms of scission and recombination mechanisms combined with reptation is now a common tool. In the past two years, there has been much agreement between experimental and theoretical work. This work includes research on shear-induced flow alignment and phase transitions, polyelectrolyte micelles, and nematic wormlike micelles.

Kinetics and mechanism of hydrogen peroxide oxidation of chromone‐3‐carboxaldehydes in aqueous acid and micellar media

Oxidation of chromone-3-carboxaldehyde (CCA) and substituted analogues by H2O2 has been carried out in aqueous acid (HCl and H2SO4) and micellar media. Reaction kinetics indicated order in [CCA] as well as [H2O2] to be unity while it is a fraction (1 > n > O) in [acid]. Reaction rates were found to be faster in the solvents of low-dielectric constant (D). Added salt (KCl or (NH4)2SO4) increased the rate of oxidation marginally. On the basis of observed linearity of Amis plot and marginal positive salt effect, protonated CCA (enol form of CCA, a cation) and H2O2 (neutral molecule) were considered as reactive species in the rate limiting step. Reaction rates were found to be enhanced significantly in anionic and nonionic micellar (sodium dodecylsulfate (SDS) and Triton X-100 (Tx), respectively) media. However, cationic micelles [cetyl trimethyl ammonium bromide (CTAB)] indicated marginal retardation effect. Effect of anionic and cationic micelles has been interpreted in terms of electrostatic interactions, while that of nonionic micelles in terms of hydrophobic interactions. Structure-reactivity correlations have been interpreted by Hammett's equation. Negative “ρ” (reaction constant) values indicated cationic transition state. © 1996 John Wiley & Sons, Inc.

Kinetics and mechanism of hydrogen peroxide oxidation of chromone-3-carboxaldehydes in aqueous acid and micellar media

Oxidation of chromone-3-carboxaldehyde (CCA) and substituted analogues by H2O2 has been carried out in aqueous acid (HCl and H2SO4) and micellar media. Reaction kinetics indicated order in [CCA] as well as [H2O2] to be unity while it is a fraction (1 > n > O) in [acid]. Reaction rates were found to be faster in the solvents of low-dielectric constant (D). Added salt (KCl or (NH4)2SO4) increased the rate of oxidation marginally. On the basis of observed linearity of Amis plot and marginal positive salt effect, protonated CCA (enol form of CCA, a cation) and H2O2 (neutral molecule) were considered as reactive species in the rate limiting step. Reaction rates were found to be enhanced significantly in anionic and nonionic micellar (sodium dodecylsulfate (SDS) and Triton X-100 (Tx), respectively) media. However, cationic micelles [cetyl trimethyl ammonium bromide (CTAB)] indicated marginal retardation effect. Effect of anionic and cationic micelles has been interpreted in terms of electrostatic interactions, while that of nonionic micelles in terms of hydrophobic interactions. Structure-reactivity correlations have been interpreted by Hammett's equation. Negative “ρ” (reaction constant) values indicated cationic transition state. © 1996 John Wiley & Sons, Inc.

Isotropic-to-nematic transition in wormlike micelles under shear

We report on the linear and nonlinear rheology of surfactant solutions of elongated wormlike micelles. The surfactant solutions placed under scrutiny are made of cetylpyridinium chloride (CP + , Cl - ) and sodium salicylate (Na + , Sal - ) diluted in 0.5 M NaCl-brine. Both semidilute and concentrated regimes of entangled micelles were investigated. Rheological experiments were performed at ambient temperature (T=25 o C) for surfactant concentrations O=1%-30%. When submitted to a steady shear high enough (for shear rate γ typically higher than 1-10 s -1 ) the solutions of wormlike micelles exhibit a first-order isotropic-to-nematic transition for all surfactant concentrations O≥6%. The transition is characterized by a true plateau in the shear rate dependence of the shear stress σ (γ). For γ above the transition rate γ 1/N , σ remains constant at σ 1/N . In the concentrated regime, the transition is clearly first-order. However, the first-order character weakens upon increasing dilution, suggesting that at some critical concentration O c it becomes second-order. Below O c , the transition ceases to occur: the σ(γ)-behavior rather indicates a progressive and homogeneous orientation of the micelles throughout the sample. Moreover, in the two-phase domain (where both isotropic and nematic phases coexist) a characteristic transient behavior of the shear stress σ (γ) measured at constant γ 1/N as a function of time has been observed and investigated in detail. In agreement with the picture of the first-order phase transition (in the domain of metastability), the transient behavior could be interpreted quantitatively in terms of nucleation and one-dimensional growth process. These results are finally compared to recent predictions by Spenley, Cates and MacLeish (Ref, [7]) who described the nonlinear rheology of wormlike micelles in terms of mechanical instability of shear-banding type

Phase behavior of the antineoplastic ether lipid [formula omitted

The physicochemical properties of the antineoplastic etherphospholipid 1-O- octadecyl-2-O- methyl- glycero-3- phosphocholine were examined in the concentration range 1–35% (w/w) lipid, as a function of temperature (range −10°C to 40°C) and of different aqueous solvents by dynamic light scattering, small- and wide-angle X-ray scattering, differential scanning calorimetry and ultrasonic speed measurements. On cooling the lipid dispersion undergoes a phase transition near 6°C, transforming slowly from a micellar into a lamellar gel phase with interdigitating hydrocarbon chains. The lamellar repeat distance is nearly constant over the hydration range 65–90% buffer ( d = 5.09–5.14 nm ). The size of the micelles in terms of the hydrodynamic radius is 3.8 ± 0.1 nm , the polydispersity is low. Their average shape is spherical. The electron density distribution across the micelle gives 2.5 nm for the extension of the hydrocarbon chains and 1.5 nm for the polar moiety. The existence of micelles was verified up to a concentration of 35% lipid. Throughout this concentration range size and shape do not change significantly. The kinetics of formation of the low-temperature phase is slow on cooling, increasing with increasing concentration. Upon heating the phase behavior shows a hysteresis. The extended lamellar organizations start to break down into smaller aggregates near 3°C. The micellar phase is reformed near 20°C.

Micellar media in kinetic determinations

Abstract The role of micellar media in analytical reaction-rate methods is discussed. The Ce(IV)As(III) reaction in the presence and absence of iodide catalyst was selected in order to study its behaviour in the presence of surfactants. Dodecyltrimethylammonium bromide (DTAB) was found to increase the reaction rate of both systems. Evidence for a “micellar catalysis” effect by DTAB is demonstrated. The analytical potential of micelles in terms of sensitivity and enhanced selectivity is also discussed.

Theoretical study of the role of head-group interactions in the micellization of non-ionic surfactants

The critical micelle concentration (c.m.c.) and various properties of amphiphiles in solution have been simulated for a simple parametrization of the free energy of formation of micelles in terms of their aggregation numbers. A simple expression for the dependence of the c.m.c. on the energy parameters is obtained empirically from the numerical determinations of the c.m.c. The criterion used for the c.m.c. is that the rate of change of monomer concentration with respect to total amphiphile concentration is at a maximum. This is compared with the results of an alternative expression based on a horizontal inflection point in the micelle size distribution (the Ruckenstein–Nagarajan criterion).Numerical results are scaled to highlight the effect of headgroup interactions, and experimental light-scattering results are simulated for a variety of systems.

Configurations of the amphiphilic molecules in micelles

Several theoretic models aim to account for the properties of micelles in terms of the configurations of the constituent amphiphilic chain molecules. Recent /sup 13/C NMR measurement of one property of the configuration distribution of the the hydrocarbon chain segments allows critical evaluation of these theories. It is concluded that the interphase and singly-bent chain theories, which fully account for chain continuity and for intermolecular constraints imposed by hydrophobic and steric forces, give a more satisfactory description of micellar molecular organization than models in which chains are ordered and radially aligned, or in which they have the complete disorder characteristic of an amorphous hydrocarbon liquid.