Pluronic Polymer Research Articles

Abstract 377: Multifunctional magnetic nanoparticles for theranostic applications

Abstract Nanoparticle technology address efficacy of cancer chemotherapy and diagnosis which can be potentially used for image guided drug delivery. Herein, we have developed a multi-layer approach for the synthesis of water-dispersible iron oxide theranostic nanoparticles for drug delivery (therapy) and magnetic resonance imaging (MRI) (diagnostic) applications. For this novel approach, iron oxide core nanoparticles were prepared by precipitation of iron salts in the presence of ammonia and coated with beta-cyclodextrin and pluronic polymer (F127). This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in beta-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and beta-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Curcumin, a cancer preventive and anti-cancer drug, loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects of this formulation were verified by examining ultra structural changes and molecular effects in cancer cells. Interestingly, F127250-CUR formulation also exhibited good haemo-compatibility. In conclusion, our data suggest that the F127250-CUR formulation can be effectively used for the delivery of anti-cancer drug drugs and cancer imaging and its potential clinical application. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 377. doi:10.1158/1538-7445.AM2011-377

A facile synthesis of mesoporous crystalline tin oxide films involving a base-triggered formation of sol–gel building blocks

We have developed a new facile procedure for manufacturing crystalline thin films of SnO2 with a uniform mesoporous architecture and full crystallinity of the walls. The procedure is based on the evaporation-induced self-assembly (EISA) of prehydrolyzed tin oxide precursor directed by a commercially available Pluronic polymer. The formation of the tin oxide precursor, which can be self-assembled into a mesoporous structure, is achieved by an addition of ammonium hydroxide to a tin tetrachloride solution. The relative concentration of ammonium hydroxide as well as the duration and temperature of the hydrolysis reaction influence significantly the properties of hydrolyzed tin oxide species and the mesostructure assembled from them. The films coated from these precursor solutions and calcined at 300 °C to 400 °C exhibit a well-developed worm-like porosity with a wall to wall distance of ca. 18 nm, a surface area of up to 50 cm2 cm(-2) (corresponding to 55±5 m2 g(-1)), and high crystallinity.

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapuetic agent for cancer therapy.

Pluronic F‐127 as the buffer additive in capillary entangled polymer electrophoresis: Some fundamental aspects

Polymeric macromolecules of well-designed structures and specific properties open promising directions in the capillary entangled polymer electrophoresis. Pluronic F-127, as a thermoassociating polymer, possesses some unique properties that can be utilized in capillary entangled polymer electrophoresis of amino acids, peptides and proteins. In this study, we studied properties of Pluronic F-127 polymer as an additive to BGE for the separation of peptides and proteins. The influence of the thermoassociation on separation selectivity was studied. The addition of Pluronic caused severe instabilities of the electrical current and the signal of the UV detector. This study reveals remarkable positive effect of a low pressure applied to the inlet buffer vial during the analysis, which apparently stabilizes the electrical current and the detector signal. The effect of hydrodynamic flow induced by the pressure applied on the separation efficiency was studied and the significance of this effect was discussed. Pluronic F-127, as a representative of synthetic macromolecules, was compared with dextran, as a representative of natural polymers, in terms of separation power, selectivity and repeatability of migration times.

Structure of magnetically guided nanocarriers of the photodithazine sensitizer from small-angle neutron scattering data

Nanosized complexes of ferromagnetic particles with a photodithazine sensitizer (used in photo-dynamic therapy in oncology) have been synthesized and investigated using small-angle neutron scattering for the first time. The structure of the complexes has been determined, and the influence of the biocompatible polymer Pluronic on their structure has been analyzed. The possibilities of using the complexes for magnetically guided delivery of the photosensitizer to cells and tissues in the treatment of oncological diseases by photodynamic therapy have been discussed.

Synthesis and characterization of mesoporous, tungsten-containing molecular sieve composites

Mesoporous, tungsten-containing molecular sieve (W-SBA-15) composites were successfully synthesized via one-step hydrothermal processing using tetraethyl orthosilicate (TEOS) as the silica precursor, sodium tungstate as the tungsten precursor, and pluronic P123 triblock polymer (EO 20PO 70EO 20, M av = 5800) as a structure-directing reagent. The influence of various synthesis factors, such as TEOS/sodium tungstate (Si/W) molar ratios, stirring solution temperatures, TEOS pre-hydrolysis time, and crystallization temperatures, on the structure of the W-SBA-15 composite were investigated. The prepared materials were characterized by using X-ray diffraction (XRD), infrared spectroscopy (IR), diffuse reflectance ultraviolet–visible spectroscopy (DR UV–vis), scanning electron microscopy (SEM), and nitrogen adsorption–desorption measurements. The results showed that all the W-SBA-15 composite materials retained the mesopore structure of SBA-15 and the tungsten oxide species successfully substituted silica in the framework.

A Multilevel Antimicrobial Coating Based on Polymer-Encapsulated ClO2

A multilevel antimicrobial coating with "release-killing", "contact-killing" and "anti-adhesion" properties was prepared from polymer-encapsulated chlorine dioxide (ClO(2)), water-in-oil-in-water (w/o/w) double emulsion. A slow sustained release of gaseous ClO(2) at a rate sufficient to inhibit bacterial growth (approximately 1300 microg of ClO(2).g(-1).day(-1)) was demonstrated for a prolonged period of time (i.e., 28 days). Touch and infectious droplets triggered an increased release of the biocides at the sites of contamination, resulting in rapid disinfection. Zinc chloride (i.e., 30 ppm) was added to provide "contact-killing" properties, while bacterial adhesion was prevented by the Pluronic polymer used to encapsulate ClO(2). The new antimicrobial coating is effective against Gram positive and Gram negative bacteria, including Bacillus subtilis , Staphylococcus aureus , and Escherichia coli. A greater than 5 log (i.e., >or= 99.999%) reduction of viable bacteria was obtained at a short contact time of 10 min.

Synthesis and structural investigation of ferrofluids with porphyrins and prospects of their application in photodynamic therapy

Complexes of superparamagnetic nanoparticles of magnetite with porphyrins, i.e., sulfonated tetraphenylporphine dihydrochloride (H2TPPS4(HCl)2) and photodithazine (used in photodynamic therapy for treatment of oncological diseases), in an aqueous medium have been synthesized for the first time and investigated using small-angle neutron scattering and spectrophotometry. The influence of the biocompatible polymer Pluronic on the functional properties of the synthesized complexes has also been analyzed. It has been shown that the synthesized complexes of ferrofluids with photodithazine and Pluronic exhibit a high efficiency as compounds capable of suppressing the reproduction of tumor cell cultures. The results obtained can be used in the design of a magnetically guided drug for photodynamic therapy.

Adsorption and catalytic activity of Porcine pancreatic lipase on rod-like SBA-15 mesoporous material

Rod-like SBA-15 mesoporous material was synthesized using amphiphilic Pluronic polymer surfactant P123 (EO 20PO 70EO 20) as structure-directing agent. The sample was characterized by SEM, TEM, SAXRD, N 2 adsorption–desorption isotherms and FT-IR spectra. It had a high specific surface area of 490 m 2 g −1, a total pore volume of 1.04 cm 3 g −1 and a pore diameter of 7.63 nm. The pore diameter was large enough for accommodating Porcine pancreatic lipase (PPL, 4.6 × 2.6 × 1.1 nm 3) molecules inside the channels. The physical adsorption immobilization of PPL on the rod-like SBA-15 mesoporous material in buffer solutions was studied via a direct one-step immobilization method. The results obtained by SAXRD and N 2 adsorption–desorption isotherms clearly showed that PPL was adsorbed into the channels of SBA-15 and the ordered mesoporous structure of SBA-15 after adsorption of PPL was retained. The catalytic activity, thermal stability, and reusability of the immobilized PPL were measured in phosphate buffer solution by hydrolysis of triacetin. The immobilized PPL showed excellent adaptability at higher pH and better thermal stability comparing with free PPL.

Study of structure properties of organized silica sorbents synthesized on polymeric templates

Mesoporous silica materials were synthesized by applying Pluronic type polymers as pore creating agents. The composition of a reacting mixture and the process conditions were changed in a synthesis procedure. These changes differentiated the characteristics of porous structure of obtained sorbents. The parameters characterizing the pore structure were estimated and the changes of pore arrangement of obtained materials being a result of different synthesis conditions were investigated. The small-angle XRD results indicate that F cubic structure was formed what confirms the cage-like ordering of the synthesized silicas.

Evaluation of Blatta orientalis (Q) nasal gel formulation in milk aspiration induced eosinophilia

Background: The purpose of the present study was to develop intranasal delivery systems of the homeopathic anti-asthmatic remedy Blatta orientalis mother tincture (Q) using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer Carbopol 934P (C934P).Methods: Formulations were modulated so as to have a gelation temperature below 34°C to ensure gelation at physiological temperature after intranasal administration. Its gelation temperature, mucoadhesive strength, viscosity and gel strength were studied. B. orientalis (Q) nasal gel was tested with recurrent milk aspiration to determine whether it produces changes in eosinophilia in a murine model of asthma.Result: The gelation temperatures of the formulations and mucoadhesive strength, determined using sheep nasal mucosal membrane, increased by the addition of increasing concentrations of Carbopol. The results of milk aspiration induced eosinophilia, B. orientalis (Q) nasal gel significantly (P < 0.001), decreased eosinophil cell count as compared with toxicant by using in absolute eosinophilia count method. Finally, histopathological examination did not detect any damage during in vivo studies.Conclusion: The PF127 gel formulation of B. orientalis (Q) with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

Synthesis and Evaluation of Amphiphilic Poly(tetrahydrofuran-b-ethylene oxide) Copolymers for DNA Delivery into Skeletal Muscle

Amphiphilic triblock copolymers such as the pluronic poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) L64 (pEO(13)-pPO(30)-pEO(13)) have been shown to mediate more efficient gene transfer in muscle as compared to naked DNA. We were interested in studying the effect of a chemical change of the central block of pluronic polymers on the transfection activity. We synthesized new amphiphilic copolymers in which the hydrophobic pPO block was replaced by poly(tetrahydrofuran) (pTHF) chains. The resulting triblock pEO-pTHF-pEO polymers have been characterized by NMR and SEC and assayed for in vitro and in vivo gene transfer. The animal experiments showed that the new copolymers are able to significantly increase the transfection efficiency of plasmid DNA after intramuscular injection. These results indicate that the capacity to enhance plasmid DNA transfection in skeletal muscle is not restricted to pEO-pPO-pEO arrangements.

Micellar crystals in solution from molecular dynamics simulations

Polymers with both soluble and insoluble blocks typically self-assemble into micelles, which are aggregates of a finite number of polymers where the soluble blocks shield the insoluble ones from contact with the solvent. Upon increasing concentration, these micelles often form gels that exhibit crystalline order in many systems. In this paper, we present a study of both the dynamics and the equilibrium properties of micellar crystals of triblock polymers using molecular dynamics simulations. Our results show that equilibration of single micelle degrees of freedom and crystal formation occur by polymer transfer between micelles, a process that is described by transition state theory. Near the disordered (or melting) transition, bcc lattices are favored for all triblocks studied. Lattices with fcc ordering are also found but only at lower kinetic temperatures and for triblocks with short hydrophilic blocks. Our results lead to a number of theoretical considerations and suggest a range of implications to experimental systems with a particular emphasis on Pluronic polymers.

Effects of Block Size of Pluronic Polymers on the Water Structure in the Corona Region and Its Effect on the Electron Transfer Reactions

Effects of constituent block size of triblock copolymers on the nature of the water molecules in the corona region of their micelles have been investigated using time-resolved fluorescence measurements. The physical nature of the water molecules in the micellar corona region of the block copolymer, Pluronic F88 ([ethylene oxide (EO)]103-[propylene oxide (PO)]39-EO103), has been studied using a solubilized coumarin dye. Solvent reorientation time and rotational correlation time have been measured and compared with another block copolymer, Pluronic P123 (EO20-PO70-EO20), which has a different composition of the constituent PO and EO blocks. It is noted that due to the presence of larger number of EO blocks in F88 as compared with P123, the corona region of the former micelle is more hydrated than that of the latter. The solvent reorientation time and rotational correlation time are found to be relatively shorter for F88 as compared with P123. This indicates that the water molecules in the corona of the F88 micelle are more labile than those of P123, which is also supported from the estimated number of water molecules associated with each EO unit, measured from the size of each type of micelle and its aggregation number. To understand the effect of block size on the chemical reactions in these microheterogeneous media, electron transfer reactions have been carried out between different coumarin acceptors and N, N-dimethylaniline donor. The electron transfer results obtained in F88 micelles have been compared with those obtained in P123, and the results are rationalized on the basis of the relative hydration of the two triblock copolymer micelles.

Thermoreversible micellization and gelation of a blend of pluronic polymers

Aqueous solutions of a blend consisting of a PEO–PPO–PEO triblock copolymer, Pluronic F127 (EO100–PO65–EO100) and a PPO–PEO–PPO triblock copolymer, Pluronic-R 25R4 (PO19–EO33–PO19) were studied. Thermoreversible micellization and gelation properties of the blend were examined as a function of temperature and molar ratio of 25R4 to F127 by means of micro DSC and rheology. The completely thermoreversible behaviors of micellization and gelation were observed for all the blend solutions with two F127 concentrations (10 and 15wt%) and various 25R4/F127 molar ratios (0–4) even though the pure 25R4 solution itself was not thermoreversible. At a given concentration of F127, three effects of 25R4 on F127 were found as follows. (a) The micellization temperature of F127 shifts to a lower temperature with increasing 25R4 content, implying a “salt-out like” effect of 25R4. (b) Beyond the primary peak for micellization a secondary peak appears due to the effect of 25R4. (c) At the molar ratio of 25R4/F127=3:1, the gelation of the 15wt% F127 solution occurs twice at low and high temperatures, respectively. When the ratio>3:1, the gelation occurs only at high temperatures. The possible mechanisms involved in these unique behaviors of micellization and gelation have been proposed and discussed. The effect of 25R4 on F127 was compared with another Pluronic polymer F108 (EO133–PO50–EO133).

Core–Satellite Heterostruture of Fe3O4–Pd Nanocomposite: Selective and Magnetically Recyclable Catalyst for Decarboxylative Coupling Reaction in Aqueous Media

Abstract Fe3O4–Pd nanocomposite having core–satellite heterostructure, prepared through the reaction of Pluronic polymer (P123, PEO19–PPO69–PEO19)-coated Fe3O4 nanoparticle and Na2PdCl4, showed high catalytic activity, selectivity, and reusability for decarboxylative coupling reactions in aqueous media.

Probing Paeonol−Pluronic Polymer Interactions by 1H NMR Spectroscopy

By using a combination of 1H NMR spectroscopy, two-dimensional heteronuclear single-quantum coherence-resolved (1)H{(13)C} and homonuclear rotating-frame Overhauser enhancement NMR correlation experiments with diffusion ordered spectroscopy (DOSY), the location and distribution of a hydrophobic drug, paeonol, have been established with respect to the methyl groups of the poly(ethylene oxide)-poly(propylene oxide) -poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer. The interaction between them is adjustable according to the different temperature-dependent hydrophilicities or hydrophobicities of the triblock copolymer components. On the other hand, such interactions influence the self-assembly properties of the block copolymer amphiphiles in solution. The amount of anhydrous methyl groups of PPO segments shows an increase with increasing paeonol concentration. It was also demonstrated that the shell-crosslinking of the Pluronic polymer has an effect in increasing the amount of anhydrous methyl groups and thus increasing the hydrophobicity of Pluronic micelles. This might be the deeper reason underlying the increase in drug-loading capacity and prolongation in release time of Pluronic micelles for drug delivery after the shell-crosslinking. Changes in self-diffusion coefficients of paeonol with varying copolymer concentrations and types were also determined by the diffusion-based NMR DOSY technique, and values of K(a), DeltaG, and n were calculated.

Preparation and properties of mixed micelles made of Pluronic polymer and PEG-PE

Mixed micelles made of Pluronic P105 (P105) and poly(ethylene glycol)–phosphatidyl ethanolamine conjugate (PEG-PE) were prepared. The interaction of Pluronic and PEG-PE was studied and the interaction parameter β and critical micelle concentration (CMC) were used to evaluate the micellar stability toward dilution. The results showed that certain mixed micelles were more stable than pure Pluronic micelles upon dilution. The mixed micelles were used to trap the poorly soluble anticancer drug camptothecin (CPT). The cytotoxicity of the CPT-loaded mixed micelles against MCF-7 cancer cell was higher than that of CPT-loaded P105 micelles and much higher than that of the free drug.

Soy protein‐based nanocomposites reinforced by supramolecular nanoplatelets assembled from pluronic polymers/β‐cyclodextrin pseudopolyrotaxanes

AbstractThe self‐assembled rigid supramolecular nanoplatelets (SN) from Pluronic polymers with various lengths of polyethylene oxide (PEO) and β‐cyclodextrin have reinforced the soy protein isolate (SPI)‐based biodegradable plastics in terms of strength and modulus but at the expense of elongation. Meanwhile, the water resistance, which limited the application of the SPI plastics, was also enhanced. The structure and properties of nanocomposites were characterized by X‐ray diffraction, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), tensile test, and water uptake test. The low loading of nanoplatelets was able to disperse into SPI matrix homogeneously, which resulted in reinforcement in nanocomposites. With an increase of nanoplatelets loading, the repulsion between nanoplatelets and SPI matrix occurred, accompanying with the formation of rectangle objects, resulted in a decrease of mechanical performance of the nanocomposites. The nanoplatelets with longest free PEO segments produced highest strength with least loss of elongation by virtue of enhanced association with SPI matrix mediated by PEO segments. Meanwhile, the nanoplatelets with moderate length of free PEO segments showed optimal water resistance. Herein, the reinforcing function of a supramolecular nanoplatelet, similar to the structure of layered silicate, was verified. © 2007 Government of Canada. Exclusive worldwide publication rights in the article have been transferred to Wiley Periodicals, Inc. J Appl Polym Sci, 2008

1H NMR Spectroscopic Investigations on the Micellization and Gelation of PEO−PPO−PEO Block Copolymers in Aqueous Solutions

The effects of temperature, polymer composition, and concentration on the micellization and gelation properties of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers in aqueous solutions were investigated by 1H NMR spectroscopy. It was found that the temperature-dependent behavior of PPO blocks, observed as changes in chemical shift, half-height width, and integral value, could be attributed as an intrinsic tool to characterize the transition states during unimer to micelle formation. The 1H NMR spectral analysis revealed that the hydrophobic part, PPO, of the Pluronic polymers plays a more significant role in the temperature-induced micellization, whereas the transitional behavior of Pluronic polymer, i.e., from micellization to liquid crystals formation, resulted in the drastic broadening of the spectral signals for the PEO, indicating that the PEO segments play a more significant role in the crystallization process. It was also observed that the temperature-dependent changes in the half-height width of the PEO -CH2- signal are sensitive to the liquid crystalline phase formation, which could be attributed to the close packing of spherical micelles at high polymer concentrations or temperatures.