Thermosensitive self‐assembly micelles from A2BA2‐type poly(N‐isopropyl acrylamide)2‐b‐Poly(lactic acid)‐b‐Poly(N‐isopropyl acrylamide)2 four‐armed star block copolymers and their applications as drug carriers

A novel A₂BA₂‐type thermosensitive four‐armed star block copolymer, poly(N‐isopropyl acrylamide)₂‐b‐poly(lactic acid)‐b‐poly(N‐isopropyl acrylamide)₂, was synthesized by atom transfer radical polymerization and characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography. The copolymers can self‐assemble into nanoscale spherical core–shell micelles. Dynamic light scattering, surface tension, and ultraviolet–visible determination revealed that the micelles had hydrodynamic diameters (D_h) below 200 nm, critical micelle concentrations from 50 to 55 mg/L, ζ potentials from ?7 to ?19 mV, and cloud points (CPs) of 34–36°C, depending on the [Monomer]/[Macroinitiator] ratios. The CPs and ζ potential absolute values were slightly decreased in simulated physiological media, whereas D_h increased somewhat. The hydrophobic camptothecin (CPT) was entrapped in polymer micelles to investigate the thermo‐induced drug release. The stability of the CPT‐loaded micelles was evaluated by changes in the CPT contents loaded in the micelles and micellar sizes. The MTT cell viability was used to validate the biocompatibility of the developed copolymer micelle aggregates. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4137–4146, 2013     

pH-Sensitive Micelles Based on Double-Hydrophilic Poly(methylacrylic acid)-Poly(ethylene glycol)-Poly(methylacrylic acid) Triblock Copolymer

pH-sensitive micelles with hydrophilic core and hydrophilic corona were fabricated by self-assembling of triblock copolymer of poly(methylacrylic acid)-poly(ethylene glycol)-poly(methylacrylic acid) at lower solution pH. Transmission electron microscopy and laser light scattering studies showed micelles were in nano-scale with narrow size distribution. Solution pH value and the micelles concentration strongly influenced the hydrodynamic radius of the spherical micelles (48–310 nm). A possible mechanism for the formation of micelles was proposed. The obtained polymeric micelle should be useful for biomedical materials such as carrier of hydrophilic drug.     

Solubilization,micellar transition and biocidal assay of loaded antioxidants in Tetronic® 1304 micelles

The current study scrutinizes the solubilization behaviour of pharmaceutically active antioxidants, namely hydrocinnamic acid (HCA), cinnamic acid (CA) and phenyl propiolic acid (PPA), in the micelles of polyethylene oxide‐polypropylene oxide (PEO‐PPO) based star‐block copolymer: Tetronic® 1304 (T1304). A correlation between the molecular orbital energy levels of PEO‐PPO units of T1304 and the active parts of the antioxidants are well explained using a simulation study. The antioxidants modulate core–shell micelles of T1304 with enhanced solubilization dependent on their unsaturation and hydrophobicity, as depicted from UV–visible spectroscopy. Antioxidants as an additive induce micellization in 5% w/v T1304 thereby modulating the phase behaviour, as indicated by the decrease in the cloud point. The cloud point results are well complemented by steady state fluorescence spectroscopy findings, depicting a decrease in critical micelle temperature due to the solubilization of antioxidants into the T1304 micelles. A significant difference between the hydrodynamic diameter (D_h) of unloaded and loaded polymer micelles with antioxidants is observed from dynamic light scattering, ensuring the solubilization of the antioxidants in T1304 micelles. These results can apparently be attributed to the interaction and the charge induced by the antioxidants on non‐ionic T1304 micelles which increase the micellar size. Furthermore, the role of unsaturation and hydrophobicity of the employed antioxidants in 5% T1304 demonstrates the solution viscosity (η) change as a function of temperature. In addition, small‐angle neutron scattering depicts the shape transition (spherical to ellipsoidal to polymersomes) with temperature. The antioxidant loaded 5% T1304 micellar systems exhibit brilliant biocidal activity against the tested microbes, suggesting their antimicrobial application. © 2019 Society of Chemical Industry     

Alkanol-Induced Micelles of a Very Hydrophilic EO–PO–EO Block Copolymer: Characterization by Spectral and Scattering Methods

The aqueous solution behavior of a PEO–PPO–PEO block copolymer (EO₁₀₃PO₃₉EO₁₀₃), was investigated in the presence of aliphatic alkanols (C₂, C₄, C₆ and C₈). The non-associated polymer chains remain extremely hydrated in water, but aggregation in the form of spherical micelles was evidenced, triggered by the interaction of polymer chains with hydrophobic alkanol. We assume that the hydrophobic interaction between the PPO block of the copolymer and alkanol promotes micellization, which increases further with the introduction of higher chain length species. The critical micellization temperature (CMT), as measured by UV–visible spectroscopy, indicates an interaction of polymer chains with the alkanol bearing a higher chain length, which triggers aggregation. The micelles were characterized by small angle neutron scattering to elucidate the size and related micellar parameters. The gradual increase in the alkanol content increases the aggregation number, though the micelles were spherical in shape. We conclude that ethanol, due to its preferential solubility in the aqueous phase, does not affect the aggregation. The alkanols with chain lengths of C₄–C₈ chain, interact with the PPO block through hydrophobic interaction and shifts the CMTs to lower values. The combined effect of inorganic salt (NaCl) and alkanols show enhanced micellar properties.     

Dissociation and thermal characteristics of poly(acrylic acid) modified pluronic block copolymers in aqueous solution

The effect of salt on the dissociation behavior of a Pluronic-polyacrylic acid penta-block copolymer (P85PAA65) was examined. The average Gibbs energy corresponding to the energy for extracting a proton from P85PAA65 copolymer chains decreased with increasing NaCl concentration, suggesting that the addition of salt favors the dissociation process. A fluorescence study showed a two-step dissociation in which the formation of polymer complexes composed of a hydrophobic core surrounded by a hydrophilic shell was observed at pH 3.7, where the hydrodynamic radius (R_h) of the micellar structure increased from 145.6 to 302 nm due to coulombic repulsion of slightly charged PAA segments. As a consequence, the pyrene's first and the third vibronic peaks (I₁/I₃) ratio increased from 1.408 to 1.580, indicating a less hydrophobic or loose-coiled conformation compared to at a higher pH. At a pH of 7.22, the dissociation of the P85PAA65 copolymer was complete, yielding a dissociated polymer chain with apparent hydrodynamic radius (R_h^app) of about 3.2 nm. A reduction of the critical micelle temperature (CMT) attributed to the hydrogen bonding between Pluronic and PAA segments was observed.     

Effect of a Hydrophilic PEO–PPO–PEO Copolymer on Cetyltrimethyl Ammonium Tosylate Solutions in Water

Cetyltrimethyl ammonium tosylate (CTAT) in water forms long flexible wormlike micelles at concentrations above 10 mM, leading to highly viscous solutions and viscoelastic stiff gels above 100 mM. In the presence of a nonmicellar hydrophilic PEO–PPO–PEO triblock copolymer F87 (TBC-F87, Total mol.wt. = 7,700, EO = 70%) these wormlike micelles RE transformed into smaller structures, as evident from a sharp decrease in viscosity and increase in specific conductance. These results are quantified by small angle neutron scattering (SANS) measurements. The PPO middle block of TBC-F87 gets inserted in the CTAT micelle, the size and total aggregation number of CTAT/TBC-F87 mixed micelles decreased but the number of TBC-F87 molecules in the mixed micelles increased with an increase in [TBC-F87]. Two break points in the typical specific conductance versus CTAT concentration plot at various [TBC-F87] amounts represent interactions between CTAT and TBC-F87. The penetration of PPO of TBC-F87 inside CTAT micelles decreases hydrophobicity of the core while the presence of PEO end blocks enhances hydrophilicity each favoring smaller micelles.     

Interactions Between an Anionic Fluorosurfactant and a PEO-PPO-PEO Triblock Copolymer in Aqueous Solutions

Surface tensions were determined for a mixture of an anionic fluorinated surfactant and a PEO-PPO-PEO triblock copolymer. The interactions between the two surfactant molecules in the mixed monolayer and the mixed micelle were studied through molecular interaction parameters (β ^σ, β ^M) and the molecule exchange energy (ε, ε _m). It was noted that synergism and strong attractive interactions took place between the anionic fluorinated surfactant and the triblock copolymer molecules in both mixed micelles and mixed monolayers, reflected by the interaction parameter values of between −10 and −18 for all mixtures investigated. Moreover, it can be seen from the value of (ε − ε _m) that when the mixture has a small amount of triblock copolymer, the formation of mixed micelle results in a greater decrease in energy than does the formation of a mixed monolayer. With an increase in the mole fraction of the triblock copolymer in the mixture, in order to obtain the lowest surface energy, surfactants tend to form mixed monolayers first, and then form mixed micelles.     

Micellization and phase transition behavior of thermosensitive poly(N-isopropylacrylamide)-poly(?-caprolactone)-poly(N-isopropylacrylamide) triblock copolymers

Thermosensitive triblock copolymers with two hydrophilic poly(N-isopropylacrylamide) blocks flanking a central hydrophobic poly(?-caprolactone) block were synthesized by atom transfer radical polymerization. Core-shell micellization of the triblock copolymers was inferred from the ¹H NMR spectra derived in two different solvent environments (CDCl₃ and D₂O). The micellar characteristics of these amphiphilic triblock copolymers were studied by pyrene fluorescence techniques, dynamic light scattering and transmission electron microscopy. The critical micelle concentrations of the triblock copolymers were in the range of 4-16 mg/L and the partition coefficients were in the range of 3.10 × 10⁴ to 2.46 × 10⁵. The mean diameters of the micelles, measured by light scattering, were between 90 and 120 nm. The temperature sensitivity of the triblock copolymers was demonstrated by the phase transition of a 250 mg/L aqueous polymer solution at the lower critical solution temperature (LCST). The enthalpy of the phase transition was determined by differential scanning calorimetry. PM3 quantum mechanical calculation method was used to understand the intermolecular interactions between the copolymer and the water molecules. A modular approach was used to simulate the phase transition observed at the LCST.     

Amphipathic polymers with stimuli‐responsive microdomains for water remediation: Binding studies with p‐cresol

Amphipathic, stimuli‐responsive water‐soluble polymers have been investigated as potential remediation agents for micellar enhanced ultrafiltration (MEUF). The systems represent divergent architectural types, a triblock ABA copolymer of PEO‐PPO‐PEO, an n‐octylamide modified poly(sodium maleate‐alt‐ethyl vinyl ether), and the transport protein, bovine serum albumin. Each type exhibits stimuli‐dependent microphase separation or domain formation in response to temperature, pH, and/or ionic strength changes. Segmental associations result in hydrophobic clusters resembling those present in small molecule surfactant micelles. The effects of such segmental aggregation on sequestration of a model hydrophobic foulant, p‐cresol, have been investigated using equilibrium dialysis. The favorable molar binding values, the large hydrodynamic dimensions of the stable polymer aggregates, and potential reversibility of foulant loading could have commercial utility in high flow rate, multiple‐pass remediation processes. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2290–2300, 1999     

Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

Synthesis of amphiphilic pseudopolyamino acid‐containing ABC‐triblock copolymers and micellar characterizations

This study describes the synthesis of amphiphilic ABC‐triblock copolymers comprising a central pseudopoly(4‐hydroxy‐L ‐proline) segment and terminal hydrophilic poly(ethylene glycol)methyl ether as well as hydrophobic poly(ε‐caprolactone) blocks. Differential scanning calorimetry, ¹H‐NMR spectroscopy, and gel permeation chromatography are used to characterize the copolymers. The thermal properties (T_g and T_ms) of the triblock copolymers depend on the composition of polymers. Larger amounts of ε‐CL incorporated into the macromolecular backbone increased T_g and T_ms. Fluorescence spectroscopy, transmission electron microscopy, and dynamic light scattering are utilized to investigate their micellar characteristics in the aqueous phase. Observations showed a higher critical micelle concentration with higher hydrophilic components in the copolymers. The micelle exhibited a core‐shell‐corona and/or vesicle shape, and the average size was less than 300 nm. Drug entrapment efficiency and drug loading of micelles depending on the composition of block polymers are also described. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Effect of end-group modification,hydrophilic/hydrophobic block ratio and temperature on the surface,associative and thermodynamic behaviour of poly(ethylene oxide)-b-poly(butylene oxide) diblock copolymers in aqueous media

This study describes the surface, micellar, associative and thermodynamic properties of four diblock oxyethylene (E)/oxybutylene (B) copolymers with different hydrophilic block ends and various hydrophilic/hydrophobic ratios in aqueous media. The copolymers were denoted DE₄₀B₁₈, TE₄₀B₁₈, E₅₆B₁₉ and E₅₆B₇. The aqueous polymer solutions at various concentrations and temperatures were investigated by surface tensiometry and dynamic and static laser light scattering. Surface tension measurements were employed to detect the critical micelle concentration (CMC) as well as to calculate the surface-active and thermodynamic parameters of adsorption at the air/water interface. CMC values were also used to calculate the enthalpy of micellization (?H ⁰ _mic), free energy of micellization (?G ⁰ _mic) and entropy of micellization (?S ⁰ _mic). Similarly, various thermodynamic parameters for adsorption at the air/water interface were also deduced. Dynamic light scattering (DLS) was used to obtain the hydrodynamic radii (r _h) and volumes (υ _h) of the micelle at different temperatures, and hence the hydrodynamic expansion parameter (δ _h) was also estimated. Likewise, static light-scattering measurements enabled us to determine various parameters of the copolymer micelles, such as the weight-average molar mass (M _w), association number (N _w), thermodynamic radius (r _t), thermodynamic volume (υ _t), anhydrous volume (υ _a) and the thermodynamic expansion parameter (δ_t). Various thermodynamic and micellar parameters obtained from light scattering show that the micelles formed are spherical in shape and have rather soft interaction potentials at low temperature but become harder at higher temperature. Based on the different experimental results obtained, it can be said that various surface, micellar and thermodynamic parameters are dependent not only on the temperature and solution conditions but also on the hydrophobic/hydrophilic ratio and the end-group composition of the polymer. Modification of the hydrophilic end group of the polymer prominently affects various micellar properties. This effect can be assigned to the difference in polarity and the intermicellar charge effect.     

Poly(allyl glycidyl ether)‐block‐poly(ethylene oxide): A novel promising polymeric intermediate for the preparation of micellar drug delivery systems

Novel diblock copolymers designed for the preparation of micellar drug delivery systems, consisting of hydrophobic poly(allyl glycidyl ether) (PAGE) and hydrophilic poly(ethylene oxide) (PEO), were prepared, and their self‐assembly into micellar structures was studied. Copolymers differing in the length of the polymer blocks were purified and characterized. These amphiphilic copolymers with narrow molecular weight distributions were prepared through the anionic polymerization of allyl glycidyl ether with PEO monomethyl ether sodium salt as the macroinitiator. The PAGE–PEO copolymer readily formed small micelles with narrow size distributions via simple dissolution in water. The addition of pendant double bonds to the hydrophobic part of the chain was intended for further covalent modifications. Catalytic hydrogenation, the radical crosslinking of the micelle core, and the addition of thiol to double bonds of the copolymer were examples of such modifications that were proved to proceed with a quantitative yield for this copolymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 201–211, 2005     

Nanostructure and hydrogen bonding in interpolyelectrolyte complexes of poly(?-caprolactone)-block-poly(2-vinyl pyridine) and poly(acrylic acid)

Nanostructured poly(?-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP)/poly(acrylic acid) (PAA) interpolyelectrolyte complexes (IPECs) were prepared by casting from THF/ethanol solution. The morphological behaviour of this amphiphilic block copolymer/polyelectrolyte complexes with respect to the composition was investigated in a solvent mixture. The phase behaviour, specific interactions and morphology were investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, optical microscopy (OM), dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelle formation occurred due to the aggregation of hydrogen bonded P2VP block and polyelectrolyte (PAA) from non-interacted PCL blocks. It was observed that the hydrodynamic diameter (D_h) of the micelles in solution decreased with increasing PAA content up to 40 wt%. After 50 wt% PAA content, D_h again increased. The micelle formation in PCL-b-P2VP/PAA IPECs was due to the strong intermolecular hydrogen bonding between PAA homopolymer units and P2VP blocks of the block copolymer. The penetration of PAA homopolymers into the shell of the PCL-b-P2VP block copolymer micelles resulted in the folding of the P2VP chains, which in turn reduced the hydrodynamic size of the micelles. After the saturation of the shell with PAA homopolymers, the size of the micelles increased due to the absorption of added PAA onto the surface of the micelles.     

Studies on Micellar Behavior of PEO‐PBO or PEO‐PBO‐PEO Copolymers,or Surface Active Amphiphilic Ionic Liquids in Aqueous Media and Exploration of the Micellar Solutions for Solubilization of Dexamethasone and its Delayed Release

The aggregation behavior of a di‐ and tri‐block copolymers of type PEO‐PBO, PEO‐PBO‐PEO, surface‐active ionic liquid (SAIL) of type 4‐dodecyl‐4‐methylmorpholinium chloride [C₁₂mmor][Cl], and 1‐dodecyl‐1‐methylpyrrolidinium chloride [C₁₂mpyrr][Cl]) in water as well as in 10 mM of a poorly water soluble dexamethasone (dex) aqueous solution was studied by determining the critical micelle concentrations using drug solubilization, surface tension, and isothermal titration calorimetry (ITC) methods. ITC measurements were also made on solutions prepared by mixing the micellar aqueous solutions of copolymers and simple aqueous solutions of SAIL across the mole fractions at three different temperatures (298.15, 308.15, and 318.15 K). The thermodynamic parameters, namely Gibbs free energy (ΔG_m), enthalpy (ΔH_m), and entropy (ΔS_m), of micellization were calculated, and it was observed that the negative ΔG_m and positive ΔS_m for the mixture solutions increase with the increase in mole fraction of SAIL. Otherwise, the micellization is reported to be a spontaneous and highly entropy‐driven process. The dex‐solubilized micellar solutions were mixed with agar to obtain standing gels. The gel samples were dry‐cast into thin films, and the release of dex from films by simple dilution was monitored by UV measurements. The drug release data was fitted to several mechanistic models, and it was inferred that the release mechanism for dex from thin films is non‐Fickian for mixtures and Fickian in copolymer or SAIL micellar aqueous solutions. The transport of dex is diffusion‐controlled with diffusivities of 5.8–12 × 10^?11 m² s^?1 for copolymer micelles, 5–11 × 10^?11 m² s^?1 for micelles of SAIL, and 3–14 × 10^?11 m² s^?1 for the mixed micelles of copolymer and SAIL in aqueous media.     

Synthesis and the effect of hydrophobic dodecyl end groups on pH-responsive micellization of poly(acrylic acid) and poly(ethylene glycol) triblock copolymer in aqueous solution

A pH-responsive triblock copolymer of poly(acrylic acid)-b-poly(ethylene glycol)-b-poly(acrylic acid) containing hydrophobic dodecyl end groups (C₁₂H₂₅-PAA-b-PEG-b-PAA-C₁₂H₂₅) with narrow molecular weight distribution (M _w/M _n?=?1.30) was synthesized via reversible addition-fragmentation chain transfer polymerization of acrylic acid (AA). Poly(ethylene glycol) (PEG) capped with S-1-dodecyl-S??-(??,????-dimethyl-????-acetic acid) trithiocarbonate (DDATC) end groups was used as the macro chain transfer agent (PEG macro-CTA) and 2,2??-azobisisobutyronitrile (AIBN) as initiator for monomer acrylic acid. The effect of the hydrophobic dodecyl end groups on pH-sensitive self-association of C₁₂H₂₅-PAA-b-PEG-b-PAA-C₁₂H₂₅ in aqueous solution was investigated by fluorescence spectroscopy, dynamic light scattering and atomic force microscope. At pH ??5.5, the solution behavior of C₁₂H₂₅-PAA-b-PEG-b-PAA-C₁₂H₂₅ is like polyelectrolyte in aqueous solution, and the effect of dodecyl end groups is negligible. At pH <5.0, the hydrophobic dodecyl end groups contribute dominantly to the pH-sensitive micellization and result in the formation of micelles with stronger hydrophobicity and larger size at low concentration (critical micelle concentration is 0.062?g/L). In the range of pH 2.5?C3.5, the steady (R _h????35.0?nm) and narrow size distributed micelles (polydispersity index, PDI?<?0.2) can be obtained. The micelles formed by C₁₂H₂₅-PAA-b-PEG-b-PAA-C₁₂H₂₅ triblock copolymer in acidic solution are expected to have a core?Cshell?Ccorona structure, where the hydrophobic dodecyl groups form the core, and weak hydrophobic PAA/PEG hydrogen-bonded complexes form the shell and the uncomplexed PAA, and PEG chain segments form the corona.     

Different drug incorporation routes in ethylene oxide based copolymers

Coumarin is successfully incorporated in poly(ethylene oxide)‐poly(propylene oxide) block copolymers functionalized with terminal alkynes, PEO‐b‐PPO‐b‐GPE, by click reactions at atmospheric pressure and in CO₂ supercritical conditions (scCO₂). The presence of glycidyl propargyl ether (GPE), an alkynyl‐terminated monomer, in the copolymer chain allows the covalent attachment of the coumarin by click chemistry, obtaining polymer–drug conjugates. First, the most suitable synthesis procedure for the above‐mentioned copolymers was established. Then, the click reactions were carried out confirming the coumarin attachment by Fourier transform IR and ¹H NMR analyses, achieving good yields in both cases with a coumarin content of about 9.3 wt% and avoiding the use of toxic solvents in the case of scCO₂. In addition, thanks to the amphiphilic character of the copolymer due to the presence of hydrophilic (PEO) and hydrophobic (PPO) segments, micelle formation is also possible and was confirmed by dynamic light scattering and high resolution SEM. Finally, coumarin incorporation was achieved by micelle formation using the direct dissolution method in order to compare the polymer–drug system properties. This second route allows a drug entrapment efficiency of 14 wt% to be reached. In both cases, the size of the polymeric micelles obtained is in a suitable range to enable permeability. However, an interesting point is the reduction in the size of the micelles with increase in the GPE percentage and with the covalent attachment of the coumarin to the copolymer, which is supposed to improve their permeability. © 2019 Society of Chemical Industry     

Incorporation of Lamotrigine Drug in the PEO–PPO–PEO Triblock Copolymer (Pluronic F127) Micelles: Effect of Hydrophilic Polymers

The hydrophobic drug Lamotrigine (LTG) shows low bioavailability after oral administration. Work has been performed to improve the aqueous solubility of LTG using the micelles of amphiphilic block copolymers. Polyethylene oxide- polypropylene oxide- polyethylene oxide triblock copolymers (PEO–PPO–PEO), known as Pluronic^®, have been the subject of current interest due to the versatile structural possibilities of varying PEO/PPO ratios. Incorporation of LTG in the aqueous micellar solutions of Pluronic^® F127 was investigated using UV–visible spectroscopy. The shapes and size of the micelles with and without LTG have been ascertained using dynamic light scattering and small angle neutron scattering experiments. Results show increase in the Pluronic^® micellar size with hard sphere radius with the incorporation of LTG. The effect of hydrophilic polymers (PEG1500 and F68) on the LTG-incorporated Pluronic^® F127 micelles was also studied and found inefficient for enhancement of the solubility of LTG. Solid forms of LTG-incorporated Pluronic^® F127 micelles with and without hydrophilic polymers, coded as LPMs, were successfully prepared through the thin-film hydration method. Fourier transform infrared spectroscopy, X-ray diffraction spectroscopy and thermogravimetric analysis have been used to ensure the compatibility of the LTG with Pluronic^® F127 micelles in prepared LPMs. All the LPMs showed good incorporation efficiency, loading capacity and the sustained release profile of LTG. Results showed no specific improvement with the addition of hydrophilic polymers in the studied concentration range.     

Preparation of liquid‐filled micelles based on an amphiphilic triblock copolymer

A series of novel amphiphilic triblock poly(ethylene glycol)‐b‐poly(2‐aminoethyl methacrylate hydrochloride)‐b‐poly(heptadeca‐fluorodecyl acrylate) (PEG‐b‐PAEMA‐b‐PHFDA) comprised of two hydrophilic PEG and PAEMA segments and one hydrophobic PHFDA segment was designed and synthesized. The structure of the triblock copolymer was characterized by ¹H‐NMR and GPC analysis. The amphiphilic triblock copolymer was capable of self‐assembling into liquid‐filled micelles that consisted of PHFDA and liquid perfluorocarbons (PFCs) as the core and PEG as outer shell. PAEMA can be used as cross‐linking sites to increase the stability of the liquid‐filled micelles. The shape, size, and Acoustic properties of the obtained liquid‐filled micelles were investigated. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Mixed Micellar and Interfacial Studies of Triblock Copolymers with Amphiphilic Drug Ibuprofen in Aqueous Urea Solutions

Mixed micellar and surface properties of non-ionic triblock copolymers (Pluronic® P123 and F68) and non-steroidal anti-inflammatory drug Ibuprofen (IBF) have been evaluated in aqueous urea (100 mM) solutions with the help of surface tension and fluorescence measurements at 298.15 K. Various bulk and surface parameters such as critical micelle concentration (CMC) of the mixtures, micellar mole fraction (X), interaction parameter (β) and free energies were calculated using Clint, Rubingh, Rosen and Maeda models. In aqueous solutions, all the mixtures show synergistic interactions and are more in mixtures of IBF with P123. These interactions decrease in presence aqueous urea solution due to breaking of water structure surrounding the hydrophobic moieties by urea molecules resulting in delayed mixed micellization. Micellar aggregation number (N_agg) obtained from the steady state fluorescence quenching indicate that the participation of triblock copolymer is more than the drug IBF in mixed micelle formation. Stern-Volmer constant (K_SV), dielectric constant (D_exp), and micropolarity (I₁/I₃) have also been evaluated and their contribution in the mixed micellar systems have been discussed.