Pluronic L64 Research Articles

Thermosensitive Interfacial Migration of 5-FU in the Microenvironment of Pluronic Block Copolymers.

Chemotherapy is one of the most important ways to treat cancer. At present, chemotherapy medicines are mainly administered by intravenous injection or oral administration. However, systemic medical care requires the dosage of high concentrations of drugs to defeat the malignant tumor growth. In recent years, the use of polymer composites for local and sustained drug release has become an important field of research to minimize side effects due to high-concentration chemotherapy drugs. Here, 19F-{1H} heteronuclear Overhauser enhancement spectroscopy (HOESY) was used to study the micellular environment of the F-containing chemotherapeutic drug 5-FU in Pluronic F127, Pluronic L121, and F127/L121 binary blending composites. The distribution of 5-FU in micelles is related to the PEO and PPO segment length of Pluronic polymers and the environmental temperature. The drug release tests further confirm that if 5-FU medicines were loaded in the PPO segment inside the micelles, the purpose of the prolonged drug release carrier is achieved.

Catalase-loaded polymersomes as a promising safe ingredient to active photoprotection

The topical application of enzymes for UV-induced damage repair, such as catalase, represents an interesting strategy for "active" photoprotection. However, catalase, a large and hydrophilic molecule, needs to penetrate the skin to present activity and, in this sense, nanocarriers can provide an aid for barrier crossing. Among the nanocarriers, polymersomes (Ps) obtained by the self-aggregation of amphiphilic block copolymers represent an alternative for topical enzyme delivery. Here, catalase-loaded Ps of Pluronic® L121, an amphiphilic triblock copolymer, were prepared by direct dissolution and in vitro evaluated regarding safety and efficacy. The Ps presented a suitable photo/cytotoxicity profile regarding the sun-damaged epidermis. Pre-clinical safety tests indicated that the HET-CAM assay was more appropriate than cytotoxicity assays to predict the irritant potential of the Ps. Based on cutaneous permeation assays associated with laser scanning confocal fluorescence microscopy, the Ps increased ten times the catalase percentage of skin permeation. Additionally, in vitro assays indicated that catalase-loaded Ps were able to eliminate UV-induced lipid peroxidation in deeper layers of the skin (viable epidermis + dermis) in comparison to free catalase. Penetration assays in 3D cell culture and efficacy assays confirmed the preferential delivery of catalase in the deeper layers of the skin owing to the permeation enhancer effect of Pluronic L121 and/or the membrane translocation capacity of the Ps. In conclusion, our findings indicate catalase-loaded Ps as an innovative nanomaterial for active sunscreens.

In-situ grown inorganic layer coated PVDF/PSF composite hollow fiber membranes with enhanced separation performance

Poly(vinylidene fluoride) (PVDF) membranes are widely employed for water treatment but mainly limited by their hydrophobic properties that increase the separation resistance. To make hydrophilic PVDF membranes, inorganic layer coated PVDF blend hollow fiber membranes are reported here. PVDF/polysulfone (PSF) blend hollow fiber membranes with pore size of ~110 nm were fabricated using PolarClean as a green solvent. Then, a facile and green method was employed to in-situ grow an inorganic layer (including TiO2 and Al2O3 layers) on these high strength membranes. Pluronic L61 was used as a dispersing agent to distribute the precursors in isopropanol, and enhanced adhesive strength between the polymer membrane and inorganic particles as characterized by XPS. The inorganic layers on the PVDF/PSF membrane surface both improved the mechanical strength from 7.7 MPa to 9.2 MPa and decreased the membrane roughness from ~50 nm to ~10 nm. The water permeance of the composite membranes can be finely tuned from 50 to 500 Lm−2h−1bar−1. In addition, the resulting membranes simultaneously enhanced the separation performance and anti-fouling performance characterized by bovine serum albumin (BSA) rejection behavior and flux recovery rate (FRR), respectively. The best BSA rejection and FRR of the PVDF/PSF-inorganic composite membranes reach 95% and 72.2%, respectively. The anti-fouling performance of composite membranes is mainly attributed to the decreased membrane roughness and enhanced hydrophilic properties compared with pristine PVDF/PSF membranes. Furthermore, the in-situ grown inorganic layers on the PVDF/PSF membrane surface effectively prevent foulants from blocking the pore channels as they are easily washed by the hydraulic washing method.

Hybrid nanoparticles based on ortho ester-modified pluronic L61 and chitosan for efficient doxorubicin delivery

Tumor intrinsic or acquired multidrug resistance (MDR) is still one of the major obstacles to the success of nanomedicine. To address this, the pH-sensitive nanoparticles (L61-OE-CS) with MDR-reversal ability were prepared by the crosslinking between acid-labile ortho-ester-modified pluronic (L61-OE) and chitosan (CS) for efficient doxorubicin (DOX) delivery. The size and micromorphology of the prepared nanoparticles were observed by dynamic light scanning and scanning electron microscopy and the nanoparticles displayed a uniform spherical shape with a diameter around 200 nm. The pH-triggered morphology change of the nanoparticles was also observed by scanning electron microscope. Drug release profiles under different pH values showed that DOX release amount within 72 h reached 16% (pH 7.4) and 76.5% (pH 5.0), respectively. In vitro cellular uptake and MTT assay demonstrated that the ortho ester and pluronic-based nanoparticles had higher cytotoxicity than non-sensitive nanoparticles. In vivo antitumor experiments also proved the superiority of the dual-functional nanoparticles, and the tumor growth inhibition rate (TGI) on day 14 was higher than 80%. Therefore, L61-OE-CS nanoparticles have great potential to be used as drug carriers in anticancer therapy.

Hydrophilic-hydrophilic mixed micellar system: effect on solubilization of drug

Mixed micellar systems have been tried with the aim of achieving higher solubility of drugs compared to single micellar systems. Hydrophobic-hydrophilic mixed micellar systems have been used for the above purpose for the drug ciprofloxacin in the past. In the present study, a hydrophilic-hydrophilic binary micellar system comprising of pluronic copolymers pluronic F127 and pluronic L64 has been studied for its effect on solubilization of the drug Ciprofloxacin. The solutions of the two individual pluronic and their mixed micellar system with drugs were subjected to characterizations viz. UV-spectrophotometry, fluorimetry, FT-IR, dynamic light scattering (DLS), rheology, and partition coefficient. The mixed pluronic–drug system displayed greater solubility of the drug compared with the neat pluronic-drug systems in most of the characterizations. New C–OH bond formation was evidenced by FT-IR spectra due to drug micelle interaction. The values of free energy changes of micellization were found to be −25 kJ mol−1 for pluronic F127, −74.5kJmol−1 for L-64, and −170.4 kJ mol−1 for the mixed pluronic. This is suggestive of spontaneous and stronger binding of drug ciprofloxacin with mixed pluronic in comparison with that in single micellar systems.Graphic abstract

Interaction between sodium dodecylsulfate (SDS) and pluronic L61 in aqueous medium: assessment of the nature and morphology of the formed mixed aggregates by NMR, EPR, SANS and FF-TEM measurements.

The interaction of copolymer L61 i.e., (EO)2(PO)32(EO)2 (where EO and PO are ethylene and propylene oxides, respectively) with surfactant SDS (sodium dodecylsulfate) in relation to their self-aggregation, dynamics and microstructures has been physicochemically studied in detail employing the Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), Small-Angle Neutron Scattering (SANS), and Freeze-Fracture Transmission Electron Microscopy (FF-TEM) methods. The NMR self-diffusion study indicated a synergistic interaction between SDS and L61 forming L61-SDS mixed complex aggregates, and deuterium (2H) NMR pointed out the nonspherical nature of these aggregates with increasing [L61]. EPR spectral analysis of the motional parameters of 5-doxyl steraric acid (5-DSA) as a spin probe provided information on the microviscosity of the local environment of the L61-SDS complex aggregates. SANS probed the geometrical aspects of the SDS-L61 assemblies as a function of both [L61] and [SDS]. Progressive evolution of the mixed-aggregate geometries from globular to prolate ellipsoids with axial ratios ranging from 2 to 10 with increasing [L61] was found. Such morphological changes were further corroborated with the results of 2H NMR and FF-TEM measurements. The strategy of the measurements, and data analysis for a concerted conclusion have been presented.

GLUT1‐Targeting and GSH‐Responsive DOX/L61 Nanodrug Particles for Enhancing MDR Breast Cancer Therapy

AbstractEfficient targeting to tumor tissues and subsequent rapid drug release in cancer cells remains a major challenge for nanodrug delivery systems. Herein, smart nanodrug particles with reduction‐sensitive and active tumor‐targeting ability are constructed based on the nanoprecipitation of glucosamine‐grafted pluronic L61 (GA‐L61) and disulphide‐linked doxorubicin dimer (DOXSSDOX) to overcome tumor multidrug resistance (MDR). These nanoparticles show proper size and excellent stability under neutral conditions, while quickly release DOX due to the breakage of disulfide bonds under reductive medium. In vitro cellular uptake and drug efflux demonstrate that L61 can efficiently increase DOX concentration in MCF/ADR resistant cells by inhibiting the function of drug resistance proteins. In vivo biodistribution reveals that glucose transporter 1 (GLUT1)‐mediated tumor‐targeting significantly improves tumor accumulation of the glucosamine‐contained nanoparticles. Finally, the combination of GLUT1‐targeting, glutathione (GSH)‐responsive, and MDR‐reversal effects in nanoparticles achieve superior antitumor effects, which can provide an efficient, safe, and economic approach for drug delivery and cancer chemotherapy.

Absorption of CO2 in lyotropic liquid crystals

Vapor–liquid equilibria data of three poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/water liquid crystals (LCs) with CO2 has been obtained up to 6 bar. The investigated LCs consist of 60% (EO)3(PO)50(EO)3 (Pluronic L81), 70% (EO)8(PO)47(EO)8 (Pluronic L92), and 70% L92-NH2. The maximum CO2 loading of the LCs was 5–13 g CO2/kg sample. Pure L81 and L92 displayed higher absorption of CO2 than the LCs. Rheology measurements revealed that the increasing viscosity of the samples decreases the CO2 loading. Water diffusion in the LCs was qualitatively investigated by nuclear magnetic resonance, confirming that free water and tightly bound water are present in the LCs.

Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.

KxWO is a Novel Ferroelectric Nanomaterial for Application as a Room Temperature Acetone Sensor.

A newly synthesized nanomaterial known as KxW7O22 (KxWO) exhibits a stable room-temperature ferroelectric property. This unique ferroelectric property has revealed that KxWO is a promising material for application in a breath sensor, which can be used for patients to monitor their daily health condition and diagnose disease at every early stage with low cost, convenience, and non-invasion. In this study, we successfully synthesized nano-structured KxWO through a low cost but high yield hydrothermal method. The sensing response of KxWO to acetone is examined based on a chemiresistive effect. For the first time, we systematically studied how material structures and the component, potassium (K), can affect KxWO-based sensing performance. The results indicate that the low temperature ferroelectric property of KxWO causes an excellent response to acetone, which is the biomarker for diabetes. The lowest detection limit can be down to 0.1 ppm and the KxWO-based sensor can operate at room temperature. In addition, the Kx component KxWO and its crystal structure also play an important role in improving its sensing performance. Our results provide advanced research in (1) exploring the study of KxWO material properties by tailoring the concentration of the potassium in KxWO and introducing the surfactant Pluronic L-121 in the growing process, and (2) optimizing KxWO sensing performance by controlling its material properties.

Experimental study on interactions occurring between Pluronics and leflunomide in solution

The influence of Pluronics L64, F68, F88 and F127 on the solubility and membrane permeability of leflunomide (LEF) in acidic and alkaline buffer solutions with physiological pHs was revealed. A noticeable increase of LEF solubility in the presence of Pluronics was revealed. It was demonstrated that the structure of Pluronics has influence on the manifestation of a solubilizing effect. Namely, more efficient solubilizers for LEF were found to be L64 and F127, having the lowest content of ethylene oxide groups in the structure and lower HLB indices in comparison with F68 and F88. The binding of LEF with the core of Pluronic micelles was proposed on the basis of the obtained 1Н NMR data. Permeability of LEF through an artificial Permeapad barrier composed of phospholipids was measured using the Franz diffusion cell. Decrease of the LEF permeability in the presence of all investigated Pluronics was detected. The location of hydrophobic fragment of LEF molecule inside the micelle leads to a decrease in the non-polar surface area and the ability of the drug to pass through the lipophilic layer of the membrane.

Complexation of Pluronic L62 (EO6)-(PO34)-(EO6)/aerosol-OT (sodium bis(2-ethylhexyl)sulfosuccinate) in aqueous solutions investigated by small angle neutron scattering.

We investigate the phase behaviours of Pluronic L62 in aqueous solution in the presence of aerosol-OT (AOT) molecules by small angle neutron scattering (SANS). The presence of AOT significantly changes the micellization phenomenon of L62 micelles in aqueous solution, including their critical micelle temperature (CMT), global size, and asphericity. The origin of these observations is attributed to the complexation between the neutral L62 surfactants and the ionic AOT molecules, which additionally provides charge to the mixed micelles: we analyse the data and extract meaningful information using the Ornstein-Zernike integral formalism. As a result, we observe that the co-micellization of L62 and AOT is very stable across a wide temperature range.

Effect of valency of cation on micellization behaviour of pluronic mixed micelle F127 and L64

In this work the effect of mono, di- and trivalent ions on the micellization and clouding behavior of mixed micellar system has been reported. A mixed pluronic micellar system constituting 0.5 wt%/0.5 wt% of pluronic F127 and L64 has been used for the investigation. The UV and Fluorescence studies were carried out using eosin yellow dye as the probe. Both studies indicate that the mixed micellar system displayed the spectral properties intermediate between the neat pluronic solutions. Also, it was observed that the spectral changes occurring were in the order trivalent > di valent > monovalent cations. The order was not strictly followed in the cloud point observation. With minimum discrepancies the clouding behavior of mixed pluronic followed the order Al3+>Mg2+>K+. Dynamic light scattering studies suggested that the addition of salt changed the particle size of the mixed micelles. This salt effect can be better explained considering the small particle size of cations, such as Na+, Mg2+, and Al3+. There was increase in diameter of mixed micelle from 42.81 nm to 54.99 nm for Na+, to 45.11 nm for Mg2+ and to 46.46 nm for Al3+. The infrared studies also indicated the spectral change of mixed micelle due to salt addition. Different ions affect the dehydration of the PPO core differently. To the best of our knowledge this is the first report of salt and cationic valence effect on mixed micellar system.

Impact of Pluronics of different structure on pharmacologically relevant properties of sulfasalazine and methotrexate

The work was focused on comprehensive evaluation and comparison of the effect of Pluronics of different architecture on the pharmacologically relevant properties of methotrexate and sulfasalazine. Solubility of drugs was measured in buffers pH = 1.6 and pH = 6.8 with variable amount of Pluronics L64, F68, F88 and F127. Solubilization capacity and micelle-water partition coefficients were estimated and analyzed. Influence of the length of poly(ethylene oxide) and poly(propylene oxide) fragments in the polymer structure on the solubilizing effect was revealed. The observed solubility increase in the presence of Pluronics follows the order F127 > F88 > F68 > L64. Interactions of methotrexate and sulfasalazine with Pluronic micelles were characterized. Binding mode and composition of micelle/drug aggregates were proposed. The effect of Pluronics on the permeability of drugs across the model barrier Permeapad™ was investigated. The decrease of the permeability coefficients was discussed in terms of the change of medium viscosity and interactions of the drugs with the micelles.

Lyotropic Liquid Crystal as an Electrolyte Additive for Suppressing Self‐Discharge of Supercapacitors

AbstractSelf‐discharge severely constrains the application of supercapacitors for long‐term energy storage because it causes decay of cell voltage and loss of energy. So far, three pathways have been proposed for the self‐discharge of supercapacitors: i) ohmic leakage, ii) diffusion‐controlled self‐discharge, iii) faradaic reactions. However, solutions for mitigating the self‐discharge of supercapacitors are limited. Here, we choose lyotropic liquid crystal (LLC) as an electrolyte additive to suppress the self‐discharge of supercapacitors through the electrorheological effect of the LLC. The LLC formed by the assembly of a triblock copolymer Pluronic L64 in ion liquid [Bmim]BF4 exhibits dielectric anisotropy and can reorient in an electric field, causing increased viscosity and slower ion diffusion of the electrolyte. It is found that, by adding 5 % (vol%) LLC into TEMABF4/acetonitrile electrolyte, the self‐discharge rate at room temperature can be decreased by 32 % compared to supercapacitors without LLC. Furthermore, the LLC could reduce the self‐discharge rate of supercapacitors even at 50 °C due to its stability in a relatively wide temperature range.

Polymeric micelles of pluronic F127 reduce hemolytic potential of amphiphilic drugs

One of the main toxicities associated to intravenous administration of amphiphilic drugs is pronounced hemolytic activity. To overcome this limitation, we investigated the anti-hemolytic properties of polymeric micelles of Pluronics, triblock copolymers of poly(ethylene oxide) and poly(propylene oxide). We studied the encapsulation of the amphiphilic compound miltefosine (HePC) into polymeric micelles of Pluronics F108, F68, F127, L44, and L64. In vitro hemolysis indicated that, among the five copolymers studied, only F127 completely inhibited hemolytic effect of HePC at 50 μg/mL, this effect was also observed for other two amphiphilic molecules (cetyltrimethylammonium bromide and cethylpyridinium chloride). To better understand this interaction, we analyzed the HC50 (concentration causing 50% of hemolysis) for HePC free and loaded into F127 micelles. Copolymer concentration influenced the hemolytic profile of encapsulated HePC; for F127 the HC50 increased relative to free HePC (40 μg/mL) up to 184, 441, 736 and 964 μg/mL, for 1, 3, 6 and 9% F127, respectively. Interestingly, a linear relationship was found between HC50-HePC and F127 concentration. At 3% of F127, it is possible to load up to 300 μg/mL of HePC with no hemolytic effect. By achieving this level of hemolysis protection, a promising application is on the view, bringing the parenteral use of HePC and other amphiphilic drugs. Additionally, small-angle X-ray scattering (SAXS) was used to asses structural information on the interactions between HePC and F127 micelles.

Synthesis, characterization, and application of chemically interconnected carbon nanotube monolithic sorbents by photopolymerization in polypropylene caps.

A facile and convenient approach for the preparation of interconnected multiwalled carbon nanotube (MWCNT) monolithic sorbents in recycled plastic caps has been developed. The method, which was based on the photopolymerization of the individual MWCNTs via the formation of a W/O medium internal phase emulsion (40/60 w/w%), provides control over the size of pores, rigidity, and the mechanical stability of the final solid. Pluronic L121 was used as a surfactant containing the water phase inside it and, consequently, the organic and non-polar phase, in which the MWCNTs and the cross-linker were trapped, remained on the outside of the droplets. Optical microscopy and scanning electron microscopy (SEM) were employed to characterize the morphology of both the emulsions and the final solids, respectively. In addition, nitrogen intrusion porosimetry was performed in order to study how the specific surface area of the final monolithic solid changed (from 19.6 to 372.2m2g-1) with the variables involved in the polymerization step. To exemplify the great sorbent potential of the synthesized material, a colorimetric assay based on the retention of methylene blue within the interconnected MWCNT monolithic structure was carried out. Finally, following the positive results, the carbon nanotube-monolithic stirred caps were applied for the determination of chlorophenols in a biological matrix such as human urine, obtaining excellent recovery values (91-98%) and good precision (5.4-9.1%) under optimized extraction conditions. Graphical abstract.

Optimization and Evaluation of Beclomethasone Dipropionate Micelles Incorporated into Biocompatible Hydrogel Using a Sub-Chronic Dermatitis Animal Model.

The current study is concerned with the development and characterization of mixed micelles intended for the dermal delivery of beclomethasone dipropionate, which is a topical corticosteroid used in the management of atopic dermatitis. Mixed micelles were prepared using thin-film hydration technique, employing different concentrations of pluronic L121 with either poloxamer P84 or pluronic F127 with different surfactant mixture-to-drug ratios. The prepared formulae were characterized concerning entrapment efficiency, particle size, and zeta potential. Two formulae were chosen for ex vivo skin deposition studies: one formulated using pluronic L121/poloxamer P84 mixture while the other using pluronic L121/pluronic F127 mixture. The optimum formula with the highest dermal deposition was subjected to morphological examination and was formulated as hydroxypropyl methylcellulose hydrogel. The hydrogel was evaluated regarding viscosity and was subjected to ex vivo deposition study in comparison with the commercially available cream Beclozone®. In vivo histopathological study was conducted for both the hydrogel and Beclozone® in order to evaluate their healing efficiency. In vivo histopathological study results showed that the prepared hydrogel successfully treated sub-chronic dermatitis in an animal model within a shorter period of time compared to Beclozone®, resulting in better patient compliance and fewer side effects.

CO₂ in Lyotropic Liquid Crystals: Phase Equilibria Behavior and Rheology.

The CO2 absorption of liquid crystalline phases of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic L92, (EO)8(PO)47(EO)8), monoethanolamine (MEA), and water, with a composition of 60% L92/10% MEA/30% water has been investigated to assess potential use in carbon capture and storage applications. Vapor–liquid equilibrium data of the liquid crystalline system with CO2 was recorded up to a CO2 partial pressure of 6 bar, where a loading of 38.6 g CO2/kg sample was obtained. Moreover, the phase transitions occurring during the loading process were investigated by small angle X-ray scattering (SAXS), presenting a transition from lamellar + hexagonal phase to hexagonal (at 25 °C). In addition, the rheology of samples with varying loadings was also studied, showing that the viscosity increases with increasing CO2-loading until the phase transition to hexagonal phase is completed. Finally, thermal stability experiments were performed, and revealed that L92 does not contribute to MEA degradation.

Preparation of macroscopic carbon nanohorn-based monoliths in polypropylene tips by medium internal phase emulsion for the determination of parabens in urine samples

A porous monolithic solid based on single-walled carbon nanohorns dahlia-like structure, produced from a medium internal phase emulsion (MIPE), was prepared in a polypropylene tip using UV energy. Thus, single-walled carbon nanohorns (SWNHs) were added to the organic phase where they polymerized in the presence of a radical initiator. A cross-linker (ethylene dimethacrylate, EDMA) was also used in order to obtain a more robust structure. On the other hand, aqueous phase was the responsible for generating the pores in the final solid being inside the droplets generated by the surfactant (Pluronic L121) used to stabilize the polymerization emulsion. Variables related to the formation of the monolithic phase including the stability and composition of emulsion mixture, size of pores, solvent flow resistance and robustness, were studied in detail. In addition, the potential of the SWNH-monolith as extractant phase was evaluated using parabens as target analytes. The LODs ranged from 1 to 7 μg L−1, while the linear range was extended up to 5000 μg L−1. The reproducibility of the extraction procedure with different batches of emulsions was acceptable with RSD values < 16% and one prepared SWNH-tip can be used for more than 100 times without apparent extraction losses. The microextraction unit yielded an enrichment factor of 20 for all analytes (extraction efficiency of 100%), with recovery values between 80% and 116% in human urine samples.