Micellization Of F127 Research Articles

Investigation of the Thermogelation of a Promising Biocompatible ABC Triblock Terpolymer and Its Comparison with Pluronic F127.

Thermoresponsive polymers with the appropriate structure form physical networks upon changes in temperature, and they find utility in formulation science, tissue engineering, and drug delivery. Here, we report a cost-effective biocompatible alternative, namely OEGMA30015-b-BuMA26-b-DEGMA13, which forms gels at low concentrations (as low as 2% w/w); OEGMA300, BuMA, and DEGMA stand for oligo(ethylene glycol) methyl ether methacrylate (MM = 300 g mol–1), n-butyl methacrylate, and di(ethylene glycol) methyl ether methacrylate, respectively. This polymer is investigated in depth and is compared to its commercially available counterpart, Poloxamer P407 (Pluronic F127). To elucidate the differences in their macroscale gelling behavior, we investigate their nanoscale self-assembly by means of small-angle neutron scattering and simultaneously recording their rheological properties. Two different gelation mechanisms are revealed. The triblock copolymer inherently forms elongated micelles, whose length increases by temperature to form worm-like micelles, thus promoting gelation. In contrast, Pluronic F127’s micellization is temperature-driven, and its gelation is attributed to the close packing of the micelles. The gel structure is analyzed through cryogenic scanning and transmission electron microscopy. Ex vivo gelation study upon intracameral injections demonstrates excellent potential for its application to improve drug residence in the eye.

Interaction between mucoadhesive cellulose derivatives and Pluronic F127: Investigation on the micelle structure and mucoadhesive performance

Systems composed of bioadhesive and thermoresponsive polymers can combine in situ gelation with bio/mucoadhesion, enhancing retention of topically applied drugs. The effect of bioadhesive sodium carboxymethylcellulose (NaCMC) and hydroxypropyl methylcellulose cellulose (HPMC) on the properties of thermoresponsive Pluronic® F127 (F127) was explored, including micellization and the mucoadhesion. A computational analysis between these polymers and their molecular interactions were also studied, rationalising the design of improved binary polymeric systems for pharmaceutical and biomedical applications. The morphological characterization of polymeric systems was conducted by SEM. DSC analysis was used to investigate the crystallization and micellization enthalpy of F127 and the mixed systems. Micelle size measurements and TEM micrographs allowed for investigation into the interference of cellulose derivatives on F127 micellization. Both cellulose derivatives reduced the critical micellar concentration and enthalpy of micellization of F127, altering hydrodynamic diameters of the aggregates. Mucoadhesion performance was useful to select the best systems for mucosal application. The systems composed of 17.5% (w/w) F127 and 3% (w/w) HPMC or 1% (w/w) NaCMC are promising as topical drug delivery systems, mainly on mucosal surfaces. They were biocompatible when tested against Artemia salina, and also able to release a model of hydrophilic drug in a controlled manner.

Hydrogen-bonded polymer complexes and nanocages of weak polyacids templated by a Pluronic® block copolymer.

We investigate the phase behavior, morphology, and temperature response of hydrogen-bonded assemblies formed by a triblock copolymer Pluronic® F127 (F127) and polycarboxylic acids of varied hydrophobicity and chain lengths. As confirmed by FTIR, the complexes of poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) with F127 at acidic pH were stabilized by multiple hydrogen bonding between carboxylic acid groups of polyacids and ether groups of F127. The colloidal stability of the polyacid/F127 complexes (their occurrence as stable dispersions, slowly coagulating dispersions or precipitates) was dependent on the composition of complexes, polyacid molecular weight and hydrophobicity, as well as temperature. For both polyacids, complexes could not be solubilized in excess of polyacids, but excess of F127 resulted in the formation of colloidally stable nanostructured clusters whose size could be controlled from tens to hundreds of nanometers by the polyacid-to-F127 ratio, temperature, and the polyacid molecular weight. Hydrophobicity of polyacids had a dramatic effect on the temperature response of Pluronic®-enriched assemblies. While PMAA suppressed the LCST behavior of F127 due to binding within the temperature-responsive PPO core of F127, more hydrophilic PAA allowed F127 micellization and supported reversible, temperature-induced re-structuring of PAA-F127 clusters. At temperatures above the LCST of Pluronic®, low-molecular-weight PAA formed nanosized dispersed complexes, in which the polyacid chains were wrapped around individual F127 micelles. Chemical crosslinking of PAA in the shells of these complexes followed by removal of the templating F127 cores resulted in easy-to-prepare monodisperse pH-responsive polymer nanocages with controllable size and swelling amplitude.

Gelation and micellization behaviors of pluronic® F127 hydrogel containing poly(isobutylcyanoacrylate) nanoparticles specifically designed for mucosal application

The aim of this investigation is to combine the advantages of pluronic® F127 hydrogels and nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) core coated with a mixture of chitosan and thiolated chitosan to design novel multifunctional formulation for mucosal application. Nanoparticles offer the advantage of being mucoadhesive while pluronic® F127 hydrogel allowed prolonged contact time onto mucosal surfaces. This work highlights an unprecedented comprehensive study on the effect of nanoparticles on gelation and micellization behaviors of pluronic® F127 using rheology and micro-calorimetry experiments. Results showed that presence of nanoparticles induced (i) smaller crystal peak of F127, (ii) a decrease of the enthalpy of F127 micellization and (iii) a non-reversibility of micelle formation (during heating ramp) and micelle melting (during cooling ramp). Together, these findings suggest that a part of F127 was not able to associate into micelles and the formation of mixed micelles containing F127 unimers and PIBCA/(chitosan/thiolated chitosan) copolymer and/or PIBCA homopolymer was suspected. The interaction of F127 unimers with nanoparticles resulted from their physical de-structuration as revealed by nanoparticle size measurement. In addition, we found that short polymerization duration of one hour induced more pronounced nanoparticle de-structuration. Twenty-four hour-polymerization of isobutylcyanoacrylate in the presence of chitosan and thiolated chitosan led to more stable nanoparticles when mixed with pluronic® F127.

Microstructure transition of hydrophilic modified ibuprofen and Pluronic copolymer F127 complexes

The effect of the aggregation state of Pluronic copolymer (PEO100–PPO65–PEO100, F127) and the concentration of hydrophilic modified ibuprofen (Ibuprofen–PEG800, IP800) on the interaction between F127 and IP800 was systematically investigated by nuclear magnetic resonance, dynamic light scatter (DLS), surface tension, and freeze-fractured transmission electron microscopy. In the solution of F127 unimers (5 °C), F127 unimers tended to wrap around IP800 micelles, and the binding model of F127 unimers to IP800 micelles transferred from wrapping around to partly threading through with increasing IP800 concentration. The latter binding model was straightly confirmed by nuclear Overhauser enhancement spectroscopy. As the aggregation state of F127 is in the beginning of the micellization (20 °C), the addition of IP800 significantly promoted the micellization of F127 to form the F127/IP800 complex with F127 micelles as the skeleton called the F127–micelle complex. The sudden decrease of the size obtained from DLS stemmed from the disruption of the F127–micelle complex and accompanying rehydration of PPO which is weaker compared with refs. The amount of IP800 to disintegrate the F127–micelle complex increased in the F127–micelle-dominated solution (40 °C) compared to that at 20 °C.

Effect of water-soluble polymers, polyethylene glycol and poly(vinylpyrrolidone), on the gelation of aqueous micellar solutions of Pluronic copolymer F127

The micellization of F127 (E98P67E98) in dilute aqueous solutions of polyethylene glycol (PEG6000 and PEG35000) and poly(vinylpyrrolidone) (PVP K30 and PVP K90) is studied. The average hydrodynamic radius (rh,app) obtained from the dynamic light scattering technique increased with increase in PEG concentration but decreased on addition of PVP, results which are consistent with interaction of the micelles with PEG and the formation of micelles clusters, but no such interaction occurs with PVP. Tube inversion was used to determine the onset of gelation. The critical concentration of F127 for gelation increased on addition of PEG and of PVP K30 but decreased on addition of PVP K90. Small-angle X-ray scattering (SAXS) was used to show that the 30wt% F127 gel structure (fcc) was independent of polymer type and concentration, as was the d-spacing and so the micelle hard-sphere radius. The maximum elastic modulus (Gmax′) of 30wt% F127 decreased from its value for water alone as PEG was added, but was little changed by adding PVP. These results are consistent with the packed-micelles in the 30wt% F127 gel being effectively isolated from the polymer solution on the microscale while, especially for the PEG, being mixed on the macroscale.

In situ photogelation kinetics of Laponite nanoparticle-based photorheological dispersions

In situ photorheology experiments were conducted to investigate the kinetics of UV-triggered photogelation of aqueous Laponite nanoparticle dispersions formulated with less than 10 wt% of a triblock copolymer (Pluronic F127) and diphenyliodonium-2-carboxylate monohydrate, a photoacid generator (PAG). We show that gelation kinetics depend strongly on solution composition and intensity of UV light used during in situ photorheology experiments. A decrease in gelation rate was observed with increasing Pluronic F127 concentrations while higher PAG and Laponite concentrations result in higher gelation rates. Changing the intensity of UV light from 100 mW cm−2 to 150 mW cm−2 at a constant composition reduced the exposure time required prior to onset of gelation by half. Finally, the effect of Laponite and PAG on the micellization of F127 was probed using differential scanning calorimetry (DSC). The results show that the presence of Laponite particles and PAG suppresses the enthalpic endotherm associated with micelle formation in solutions containing up to 7.2 wt% Pluronic F127. Using these results, we present a detailed mechanism for the photogelation phenomenon as well as the parameters surrounding intelligent design and formulation of these systems.

Understanding the structure and stability of paclitaxel nanocrystals

Previously, PTX/Pluronic F127 nanocrystals were prepared in our laboratory using the stabilization of nanocrystals (SNC) method. For PTX nanocrystals, dosages could be increased to yield improved antitumor activity over Taxol ® without incidence of acute toxicity. The objectives of this current study are to further understand the structure and stability of PTX nanocrystals. More Pluronic F127 surfactant was added in the formulation to attempt to further stabilize the nanocrystals against thermal induced aggregation. However, this resulted in formation of micelles that worsened the stability of nanocrystals. The F127 desorption experiment suggested different surfactant adsorption affinity to nanocrystal surface below and above the CMC. Below the CMC monomers bound to nanocrystal surface with high affinity, but above the CMC low affinity surfactant aggregates readily left the surface upon dilution. At higher temperature the tendency of F127 micellization is enhanced due to drastically lower CMC. Consequently, at 37 °C there was F127 desorption even for nanocrystals prepared with low amounts of F127 (1:5 (w/w) PTX/F127). To improve the stability of nanocrystals, re-nanonization by incubation–sonication procedure was used to disrupt the preferred crystal growth pattern of PTX. Furthermore, we have demonstrated that a higher heating temperature (45 °C vs. 37 °C) used in the incubation–sonication procedure was able to provide even better nanocrystal stability for long periods of incubation time.

Solubilization of Ibuprofen in Pluronic Block Copolymer F127 Micelles

We studied the effect of Pluronic F127 micelle solution on the solubility of ibuprofen (IBU). The critical micelle concentration (cmc) of F127 in both water and 0.01 mol·L-1 pH 7.4 phosphate buffer salt (PBS) solution at different temperatures was determined by the pyrene fluorescence method. The concentration of the solubilized IBU was determined using high-performance liquid chromatography (HPLC). We calculated the solubility descriptors (molar solubilization capacity, χ, and micelle-water partition coefficient, K). The influences of temperature, medium properties, and additional copolymer F68 on the micellization of F127 and the solubilization of IBU were also investigated. The results showed that the solubility of IBU increased linearly with an increase in the F127 mass fraction. With an increase in temperature, a significant decrease in the cmc was apparent and a less polar microenvironment was present in the micelle core. Slight increases in χ and K were found with an increase in temperature. The cmc of F127 in PBS solution was much less than that in water, χ was essentially the same and K decreased significantly in PBS solution. F127 micelle property and the solubilization capacity of the F127 micelles were only slightly affected in the presence of F68. An analysis of the solubility descriptors indicates that the K is particularly unique for the drug IBU, and the χ is useful in determining the solubility effectiveness of copolymer F127. We also demonstrated that IBU was predominantly in the micelle core and core-corona interface.

A concise analysis of the effect of temperature and propanediol-1, 2 on Pluronic F127 micellization using isothermal titration microcalorimetry

This article aims to explore the possibility of using isothermal titration microcalorimetry (ITC) for the investigation of F127 micellization and to study the effect of temperature and addition of propanediol-1,2 on F127 micellization behavior. From this work, ITC proved efficient to be used as a tool for the determination of the critical micellization concentration (CMC) and the enthalpy of micellization (Δ H mic) of F127, from which the other thermodynamic parameters were calculated (free energy (Δ G mic), entropy (Δ S mic), and heat capacity of micellization (Δ C p,mic)). The micellization of F127 was confirmed to be a strongly endothermic process with predominance of hydrophobic interactions ( TΔ S mic > Δ H mic) and the correlation of enthalpy and entropy of micelle formation exhibits an excellent linearity. The temperature dependence of F127 micellization was revealed by using ITC, since the CMCs values were, respectively, 0.197, 0.095, 0.085, and 0.079 mM for temperatures 28, 29, 30, and 31 °C. Secondly, by the addition of propanediol-1,2 to the micellization medium containing 1.187 mM of F127, the CMC was shifted to lower values (0.095, 0.081, 0.077, 0.069 and 0.066 mM, respectively, for propanediol-1,2 concentrations of 0%, 1.4%, 2.3%, 2.8%, and 3.7% w/v in the micellization medium). Finally, ITC was used as diagnostic tool with the aim of checking the reproducibility of the experiments independently on the kinetic and the dynamic aspects related to the micelle formation breakup. However, in this work we proved that the use of ITC for the determination of the CMC and thermodynamic parameters associated with F127 micellization is limited to a range of temperatures when sigmoidal curves were obtained.

Ultrasonic velocity and light-scattering studies on the polyoxyethylene—polyoxypropylene copolymer Pluronic F127 in aqueous solution

Ultrasonic velocity and light-scattering measurements on aqueous solutions of the ABA polyoxyethylene-polyoxypropylene block copolymer, Pluronic F127, have clearly indicated a micellar mode of association over the temperature range 10–40°C. The extent of association was limited below 25°C but increased markedly at higher temperatures giving micelles with a mean weight-average aggregation number of 44 at 40°C. A pronounced decrease in the critical micelle concentration accompanied the micellar enlargement. Aggregates were asymmetric at low temperatures but increased in symmetry with temperature increase becoming spheroidal above 25°C. A theoretical treatment of the concentration-dependent changes in ultrasonic velocity is proposed from which information concerning the volume change on micellization may be obtained. Micellization of F127 over the temperature range 20–30°C has been shown to be associated with a very small change in the molar volume of the monomers and this volume change decreased with increases in temperature to the extent of 2%/°C. The temperature-dependent changes in micellar properties have been related to the reversible thermal gelation of this block copolymer.