Pluronic F127 Content Research Articles

Fabrication and characterization of ophthalmically compatible hydrogels composed of poly(dimethyl siloxane-urethane)/Pluronic F127

The novel poly(dimethyl siloxane-urethane)/Pluronic hydrogel was fabricated to develop a new ophthalmically compatible material. In this study, the soft segment consists of poly(dimethylsiloxane) dialkanol having hydroxyethyl propoxy end groups and hard segment consists of isophorone diisocyanate (IPDI). The poly(ethylene glycol) methacrylate (PEGMA) was added as the chain-extender to form UV-curable silicone marcomer. Finally, the semi-interpenetrating network (semi-IPN) hydrogel was achieved by reacting with silicone marcomer and Pluronic F127 triblock copolymer under UV-photopolymerization (mSi–PU/F127). It was found that the increase in Pluronic F127 content led to decreased water contact angle and increased the water content of silicone hydrogels. Elastic modulus also decreased with Pluronic F127 content, while surface roughness did not significantly differ from silicone controls. The Pluronic F127 content reached 4%, the apparent protein adsorption amount decreased about 60% in comparison with that of mSi–PU control. It indicated that the mSi–PU/F127 hydrogel membrane had an excellent ability to resist protein adsorption. Additionally, the oxygen permeability ( Dk) would decrease 24%, as compared with mSi–PU control. Furthermore, these hydrogel membranes were regarded as non-cytotoxic through in vitro L929 fibroblasts proliferation assay. Overall results demonstrated that the mSi–PU/F127 semi-IPN hydrogel provided silicone hydrogel materials not only having relatively high oxygen permeability and a relatively low modulus, but also enhancing hydrophilicity and anti-protein adsorption.

Novel Behavior of Heat of Micellization of Pluronics F68 and F88 in Aqueous Solutions

It is well understood that the heat of micellization for surfactants is monotonically decreased along with an increase in temperature. However, this behavior for polymeric surfactants has never been carefully examined. In this study, the heat of micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers (Pluronics F68 and F88) in water as a function of temperature is carefully examined by using a high-sensitivity differential scanning calorimeter (HSDSC). The critical micelle temperature (CMT) decreases along with an increase in the concentration of Pluronic F68 (or F88). The heat of micellization decreases along with an increase in the temperature, as expected, when the CMT is higher than 55 and 42 degrees C for Pluronics F68 and F88, respectively. It is interesting to observe that the heat of micellization increases along with the temperature while the temperature is below 55 and 42 degrees C for Pluronics F68 and F88, respectively. The enthalpy-entropy compensation phenomenon for the micellization of Pluronics F68 and F88 in connection with the hydrophobicity is discussed.

Enhanced desulfurization performance and swelling resistance of asymmetric hydrophilic pervaporation membrane prepared through surface segregation technique

The severe swelling behavior of most hydrophobic membranes has always been an obstinate problem when separating organic mixtures by pervaporation. In some cases, hydrophilic membranes may be an appropriate alternative. In this study, amphiphilic copolymer Pluronic F127 was employed as a surface modifier to fabricate polyethersulfone (PES) asymmetric pervaporation membranes via surface segregation. The scanning electron microscopy (SEM) photographs showed an asymmetric structure of PES/Pluronic F127 membranes. The Fourier transform-infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements confirmed the hydrophilic modification of the membrane surface. Based on the distinct difference of solubility in water between thiophene and n-octane, the prepared membranes were utilized to remove thiophene from n-octane by pervaporation. The effect of Pluronic F127 content on the pervaporation performance was evaluated experimentally. It has been found that both the permeation flux and enrichment factor exhibited a peak value of approximately 60 wt% of the Pluronic F127 content. The highest enrichment factor was around 3.50 with a permeation flux of 3.10 kg/(m 2 h) for 500 mg/L sulfur in the feed at 30 °C. The influence of various operating parameters on the pervaporation performance was extensively investigated.

Fluorescence spectroscopy of a naturally occurring carbazole alkaloid: murrayanine

The fluorescence properties of a naturally occurring carbazole alkaloid, murrayanine, have been studied in various polar solvents and micellar systems. It was found that fluorescence peak position and intensity are extremely sensitive to the nature of the solvent medium. Murrayanine fluorescence has been further utilized to determine the critical micellization concentration of Pluronic F68, an amphiphilic copolymer with potential applications in drug-delivery. Time-resolved fluorescence and fluorescence anisotropy decay of murrayanine measured in several n-alcohols display a monotonic retardation with increasing chain-lengths of the alcohols.

Pluronic-coated carbon nanotubes do not induce degeneration of cortical neurons in vivo and in vitro

Carbon nanotubes (CNTs) are nanodevices with important potential applications in biomedicine such as drug and gene delivery. Brain diseases with no current therapy could be candidates for CNT-based therapies. Little is known about toxicity of CNTs and of their dispersion factors in the brain. Here we show that multiwall CNTs (MWCNTs) coated with Pluronic F127 (PF127) surfactant can be injected in the mouse cerebral cortex without causing degeneration of the neurons surrounding the site of injection. We also show that, contrary to previous reports on lack of PF127 toxicity on cultured cell lines, concentrations of PF127 as low as 0.01% can induce apoptosis of mouse primary cortical neurons in vitro within 24 hours. However, the presence of MWCNTs can avoid PF127-induced apoptosis. These results suggest that PF127-coated MWCNTs do not induce apoptosis of cortical neurons. Moreover, the presence of MWCNTs can reduce PF127 toxicity.

Synthesis of highly ordered and worm-like mesoporous TiO 2 assisted by tri-block copolymer

A highly ordered and worm-like mesoporous TiO 2 materials have been prepared by evaporation-induced self-assembly method (EISA) using different concentrations of tri-block copolymer Pluronic F127 as a structure-directing agent and inorganic chlorides as precursors in a non-aqueous medium. The characterization of the mesoporous TiO 2 was carried out using small angle X-ray diffraction (SAXD), transmission electron microscopy (TEM) and N 2 adsorption/desorption. The well-ordered mesoporous TiO 2 showed average pore size of 2.8–3.7 nm and high specific area of 263 m 2/g. From TEM observation, the pore pore-wall is composed of nano-crystalline TiO 2 domains after successfully synthesized at 573 K. The pore morphology changed from well-ordered to worm-like as the concentration of Pluronic F127 increased beyond 8.35%.

Pluronic Additives: A Solution to Sticky Problems in Digital Microfluidics

Digital microfluidics (DMF) is a promising technique for carrying out miniaturized, automated biochemical assays in which discrete droplets of reagents are actuated on the surface of an array of electrodes. A limitation for DMF is nonspecific protein adsorption to device surfaces, which interferes with assay fidelity and can cause droplets to become unmovable. Here, we report the results of a quantitative analysis of protein adsorption on DMF devices by means of confocal microscopy and secondary ion mass spectrometry. This study led us to a simple and effective method for limiting the extent of protein adsorption: the use of low concentrations of Pluronic F127 as a solution additive. This strategy has a transformative effect on digital microfluidics, facilitating the actuation of droplets containing greater than 1000-fold higher protein concentrations than is possible without the additive. To illustrate the benefits of this new method, we implemented a DMF-driven protein digest assay using large concentrations (1 mg/mL) of protein-substrate. The use of Pluronic additives solves a sticky problem in DMF, which greatly expands the range of applications that are compatible with this promising technology.

The fate of Pluronic F‐68 in chondrocytes and CHO cells

The surfactant Pluronic F-68 (PF-68) is widely used in large-scale mammalian cell culture to protect cells from shear stress that arises from agitation and gas sparging. Several studies suggested that PF-68 is incorporated into the cell plasma membrane and could enter the cells, but without providing any direct evidence. The current study has examined this question for two cell types, one of pharmaceutical interest (CHO cells) and the other of biomedical interest (chondrocytes or cartilage cells). A fluorescent derivative of PF-68 was synthesized to detect and localize internalized Pluronic with culture time. PF-68 uptake by the cells was quantified and characterized. We clearly demonstrate that PF-68 enters the cells, and possibly accumulates in the endocytic pathway. CHO cells showed an average uptake of 11.7 +/- 6.7 (SEM) microg PF-68/10(6) cells while the uptake of chondrocytes was 56.0 +/- 10.9 (SEM) microg PF-68/10(6) cells, independently of the initial PF-68 concentration (between 0.01 and 0.2%, w/v) and of cell concentration (from 1 x 10(6) to 4 x 10(6) cells/mL). These uptake values were identical for both static and agitated culture conditions. Finally, we found that CHO cells are able to eliminate intracellular fluorescent PF-68 but chondrocytes are not. These results show that the uptake of PF-68 by the cells can severely affect PF-68 concentration in the culture medium and thus shear protection effect.

Fabrication of antifouling polyethersulfone ultrafiltration membranes using Pluronic F127 as both surface modifier and pore-forming agent

Amphiphilic copolymer Pluronic F127 was used as multifunctional additive to fabricate antifouling polyethersulfone (PES) ultrafiltration membranes. The scanning electron microscopy (SEM) photographs showed an asymmetric morphology of PES/Pluronic F127 membranes. The static water contact angle measurements and X-ray photoelectron spectroscopy (XPS) analysis confirmed surface hydrophilic modification of the membranes. The protein rejection experiments indicated that the pore sizes of the skin layer were enlarged with the increase of Pluronic F127 content. The dual role of Pluronic F127 as surface modifier and pore-forming agent was distinctly observed and tentatively analyzed. During the dissolution and subsequent coagulation process, some Pluronic F127 molecules are bound to and/or tangled with PES chains due to the presence of hydrophobic PPO blocks, and then spontaneously segregate to the membrane/water interfaces due to the presence of hydrophilic PEO blocks. Meanwhile, the majority of Pluronic F127 molecules self-assemble into spherical micelles with core/shell configuration. These micelles are extracted into the coagulation bath during the coagulation process and the spaces they once occupied will turn into the pores of the membranes. In summary, a facile method for fabricating a series of PES/Pluronic F127 membranes with controlled flux and excellent antifouling property was developed.

Enhanced permeation performance of cellulose acetate ultrafiltration membrane by incorporation of Pluronic F127

Modified cellulose acetate (CA) ultrafiltration membranes were prepared using Pluronic F127 block copolymer as both pore-forming agent and surface modification agent. The water content of modified CA membranes increased with an increase of Pluronic F127 content in the casting solutions. The scanning electron microscopy (SEM) photographs showed that the modified CA membranes had thinner top layer and bigger pore volume in the porous sub-layer compared to the CA control membrane. The decrease of static water contact angle with an increase in Pluronic F127 content indicated an increase of surface hydrophilicity. The results of Fourier transform infrared spectrometer (FT-IR) analysis confirmed that most of Pluronic F127 has been leached out from the modified CA membranes. The ultrafiltration experiments revealed that the addition of Pluronic F127 influenced the permeation performance of the membranes, all the modified CA membranes exhibited higher water flux and higher bovine serum albumin (BSA) rejection ratios than those of the CA control membrane.

Sertaconazole-HPβCD-pluronic F127 solid inclusion complexes: characterization and effect on drug solubility

The influence of Pluronic® F127 (PF127) on hydroxypropyl-β-cyclodextrin (HP-βCD) complexation in solid state with sertaconazole, a highly active but poorly soluble antifungal drug, and its repercussion on drug solubilization and release rate were evaluated. Solid ternary systems comprising sertaconazole: HP-βCD:PF127 were obtained by (i) kneading of blends wetted with methanol:phosphate buffer; (ii) freeze-drying of filtered suspensions; and (iii) cast of films of filtered suspensions in an oven at 37°C. Two levels of PF127 concentrations were evaluated, one below (0.1%) and other above (5%) the critical micellar concentration (CMC). Physical mixtures were used as references. Differential scanning calorimetry, Raman spectroscopy and X-ray difractometry showed that PF127 did not significantly interfere in the complexation process, as confirmed by the total amount of sertaconazole nitrate (SN) dissolved. Nevertheless, the presence of 5% PF127 significantly delayed the release owing to its ability to form a gel layer. These ternary systems are potentially useful to combine drug solubilization ability with control of drug release.

Determination of Drug and Fatty Acid Binding Capacity to Pluronic F127 in Microemulsions

We propose that one can deduce very insightful information regarding the drug and fatty acid binding capacity of microemulsions through simple turbidity experiments. Pluronic F127-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated amitriptyline, an antidepressant drug. We observed that, above certain Pluronic F127 concentrations, turbidity was never observed, irrespective of how much amitriptyline was added to the microemulsion. We also observed that whenever sodium caprylate fatty acid was not included in the microemulsion formulation, turbidity never occurred. On the basis of these findings, we were able to determine the point at which all sodium caprylate present in the microemulsion formulation was bound to the F127 in the microemulsion (i.e., no fatty acid was free in the bulk in monomer form). By the same logic we were also able to determine how much amitriptyline was binding to the microemulsions. We also measured the dynamic surface tension, foamability, and fabric wetting time of the microemulsion formulations to further prove the hypothesis that all fatty acid is bound to the F127 in the microemulsion above a critical Pluronic F127 concentration. On the basis of this research, we have concluded that there are approximately 11 molecules of sodium caprylate fatty acid bound per molecule of Pluronic F127 and approximately 12 molecules of amitriptyline bound per molecule of Pluronic F127 in the optimal microemulsion formulation. These findings give us valuable information about the charge density at the oil/water interface and about the mechanism of binding of the drug to the microemulsion.

Drug Solubilization and Delivery from Cyclodextrin-Pluronic Aggregates

Colloidal systems based on Pluronic F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPbetaCD was evaluated by surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 degrees C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher values by the addition of 38.17 mM HPbetaCD (CMC(app) = 1.18 mM). This is related to the threading of HPbetaCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPbetaCD at this concentration notably raised the sol-gel transition temperature; the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPbetaCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPbetaCD concentrations below 80 mM, an additive effect of both components on SN solubility was observed. At greater HPbetaCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPbetaCD molecules, decreasing the total number of micelles and HPbetaCD cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPbetaCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 degrees C.

FORMULATION AND EVALUATION OF CROCONAZOL HYDROCHLORIDE TOPICAL GELS

This study was designed to evaluate different polymers for their suitability as a vehicles for topical drug delivery systems. Croconazol hydrochloride is an azol derivative used as antimycotic agent. It was incorporated in this vehicles as a gel forms in a concentration of 1.0% w/w. Polymers used in this study are methylcellulose (MC), Tylose (Ty), Polyvinyl alcohol (PVA), Pluronic F-127 (pl. F-127), Polyethylene glycol (PEG), Carbopol 974P (Carb.) and Eudispert mv. (Eud). They were used in a suitable concentration for gel formulation. In-vitro release characteristics of the drug from different gels were carried out using dialysis membrane in phosphate buffer pH 5.2. The release data were treated with various kinetic principles to assess the relevant parameters. The general rank order of Croconazol hydrochloride release from the prepared gel were MC > Ty > pl. F-127 > PVA > Carb > Eud > PEG. The results showed that, the release of drug from the prepared gels obeyed the diffusion model (Higuchi’s equation). Some kinetic parameters were calculated such as diffusion coefficient, permeability coefficient and the partition coefficient. The results indicated a direct dependence of the release rate on the diffusion coefficient. The influence of initial drug concentration (0.5, 1.0 and 2.0% w/w), and pl F-127 concentration (20, 25, 30% w/v) on the release patterns was studied. The obtained data revealed an inverse correlation between the drug release rate and the pluronic F-127 concentration and a direct correlation between the drug release rate and the initial drug concentration. The anti-fungal activity of the different gel formulations was evaluated by agar-cup plate technique using five fungal species. The results obtained indicated that, all gel formulations have good anti-fungal activities.

Remarkable Reduction of Irreversible Fouling and Improvement of the Permeation Properties of Poly(ether sulfone) Ultrafiltration Membranes by Blending with Pluronic F127

Hydrophilic modification of ultrafiltration membranes was achieved through blending of Pluronic F127 with poly(ether sulfone) (PES). The chemical composition and morphology changes of the membrane surface were confirmed by water contact angle, X-ray photoelectron spectroscopy, scanning electron microscopy, and protein adsorption measurements. The decreased static water contact angle with an increase in the Pluronic F127 content indicated an increase of surface hydrophilicity. XPS analysis revealed enrichment of PEO segments of Pluronic F127 at the membrane surface. The apparent protein adsorption amount decreased significantly from 56.2 to 0 microg/cm(2) when the Pluronic F127 content varied from 0% to 10.5%, which indicated that the blend membrane had an excellent ability to resist protein adsorption. The ultrafiltration experiments revealed that the Pluronic F127 content had little influence on the protein rejection ratio and pure water flux. Most importantly, at a high Pluronic F127 content membrane fouling, especially irreversible fouling, has been remarkably reduced. The flux recoveries of blend membranes reached as high as 90% after periodic cleaning in three cycles.

Quantitative studies of cell-bubble interactions and cell damage at different pluronic F-68 and cell concentrations.

Pluronic F-68 (PF-68) is routinely used as a shear-protection additive in mammalian cell cultures. However, most previous studies of its shear protection mechanisms have typically been qualitative in nature and have not covered a wide range of PF-68 and cell concentrations. In this study, interactions between air bubbles along with the associated cell damage were investigated using the novel adenovirus-producing cell line PER.C6, a human embryonic retinoblast transfected with the adenovirus type 5 E1 gene. A wide range of PF-68 and cell concentrations (approximately 3 orders of magnitude) were used in these studies. At low PF-68 concentrations (0.001 g/L), cells had a very high affinity for bubbles, indicated by a more than 10-fold increase in cell concentration in the foam layer liquid versus the bulk liquid. At high PF-68 concentrations ( approximately 3 g/L), however, the cell concentration in the foam layer liquid was only approximately 40% of that in the bulk cell suspension. The number of cells associated with each bubble decreased from approximately 1000 cells at 0.001 g/L PF-68 to approximately 120 cells at 3 g/L PF-68. Despite the lower cell affinity for bubbles at a high PF-68 concentration, at high cell concentrations (10(7) cells/mL and 1 g/L PF-68) significant cell entrapment occurred in the foam layer, on the order of 1000 cells/bubble. For the cells carried by the bubbles, quantitative cell damage data revealed that the probability of cell death from bubble rupture was independent of bulk cell concentration but was affected by PF-68 concentration. These quantitative studies further indicated that even at a low PF-68 concentration of 0.03 g/L, approximately 30% of the attached cells were killed during the bubble rupture process. At the same time, at low PF-68 concentration (<0.1 g/L), significant cell death occurred prior to bubble rupture. On average, a bubble disrupted more cells in the bulk liquid and/or foam layer than during rupture. For both mechanisms, the number of cells damaged by each bubble increased with decreasing PF-68 concentration and increasing bulk cell concentration.

In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate

The purpose of this study was to develop Pluronic F127 (PF127) based formulations of timolol maleate (TM) aimed at enhancing its ocular bioavailability. The effect of isotonicity agents and PF127 concentrations on the rheological properties of the prepared formulations was examined. In an attempt to reduce the concentration of PF127 without compromising the in situ gelling capabilities, various viscosity enhancing agents were added to PF127 solution containing 0.5% TM. The viscosity and the ability of PF127 gels to deliver TM, in vitro, in absence and presence of various viscosity enhancing agents were also evaluated. At the used concentration, some of the examined isotonicity agents had effect on the viscosity of TM gel. However, the viscosity of gel increased as the PF127 concentrations increased. The viscosity of formulations containing thickening agents was in the order of PF–MC 3%>PF–HPMC 2%>PF–CMC 2.5%>PF127 15%. The slowest drug release was obtained from 15% PF127 formulations containing 3% methylcellulose. In vivo study showed that the ocular bioavailability of TM, measured in albino rabbits, increased by 2.5 and 2.4 fold for 25% PF127 gel formulation and 15% PF127 containing 3% methylcellulose, respectively, compared with 0.5% TM aqueous solution.

Studies of the shear protective effects of Pluronic F-68 on wild carrot cell cultures

Numerous studies have confirmed that Pluronic F-68 can effectively protect mammalian cell cultures grown in intensely agitated bioreactors from the damaging effects of hydrodynamic shear. Like mammalian cells, plant cells exposed to intense shear conditions are also severely damaged. However, the possibility of shear-protection for plant cells by Pluronic F-68 (PF-68) is seldom addressed. This work addressed this deficiency and investigated the shear-protective properties of PF-68 on wild carrot cultures ( Daucus carota), using a two-level, three-factor (2 3) factorial design. The aim of the experiments was to determine whether PF-68 could provide similar protection for plant cells compared to animal cells, using a novel shearing apparatus [Chem. Eng. Res. Des. 79 (2001) A8]. The three factors involved in the study were impeller speed (300, 400 rpm), exposure time (3, 4 h) and the concentration of the proposed shear-protective agent—PF-68 (0.05, 0.1%, w/v). As biological responses of plant cells change exponentially with shear stress and time, narrow ranges of the speed and exposure time were necessary to ensure the linearity of the results. The biological responses of the plant cells were quantified as relative mitochondrial activity, aggregate size and membrane integrity. Student’s t-tests confirmed a significant improvement in the biological responses for the cell cultures grown in a medium supplemented with PF-68. Cell breakage was reduced considerably for cells grown in medium supplemented with PF-68. The principal variables affecting growth were agitator speed and time. In addition, the mitochondrial response showed strong interactions between concentration, shear and exposure time. These interactions implied that the concentration of PF-68 providing optimal protection may depend on the shear conditions.

Measurement of hydrophobic interactions of mammalian cells grown in culture

An assay was developed to measure the hydrophobic interactions of commonly used mammalian cell lines grown in culture. The assay depends on the loss of cells from an aqueous suspension following vortexing with a hydrophobic oil phase. This allowed the determination of a hydrophobicity index, which was significantly higher for Chinese Hamster Ovary (CHO) cells than either a murine hybridoma (CC9C10) or a myeloma (SP2/0). This suggests that CHO cells may have a higher intrinsic cell surface hydrophobicity. The assay was also used to study the effect of different additives on the hydrophobic interactions of the cells. A dose-dependent effect was shown for the non-ionic surfactant, Pluronic F68, in reducing the hydrophobic interaction of the CHO cells. However, the pattern of the decrease due to Pluronic F68 was different for each cell line. A higher concentration of Pluronic F68 (0.2%) was required to eliminate the hydrophobic interactions of CHO cells compared to either myelomas or hybridomas, where only 0.05% was required to reduce these interactions to a similar level. Several oils were found suitable for this assay although canola oil maximized the sensitivity of the measured changes. The assay may be useful in monitoring changes in the hydrophobic interactions of mammalian cells during growth in bioreactors. This may be important in optimizing the concentration of cell protectants such as Pluronic F68 in agitated cultures.

Stability of Cefazolin in Pluronic F-127 Gels

As a part of studies on the possible application of pluronic F-127 gels for drug delivery systems, an investigation was carried out to characterize cefazolin stability in aqueous pluronic F-127 gels. Pseudo-first-order rate constants for the cefazolin degradation were obtained from different concentrations of pluronic F-127 gels at temperatures of 35°, 45°, and 55°C. Rate measurements were also carried out in the gels composed of different pluronic F-127 concentrations (20%, 25%, and 30% w/v).