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.     

Effect of chain lengths of PEO-PPO-PEO on small unilamellar liposome morphology and stability: an AFM investigation

The morphology and stability of small unilamellar egg yolk phosphatidylcholine (EggPC) liposomes modified with the Pluronic copolymer (poly (oxyethylene)-poly (oxypropylene)-poly (oxyethylene) (PEO-PPO-PEO)) with different compositions on mica surface have been investigated using atomic force microscopy. Morphology studies reveal significant morphological changes of liposomes upon incorporating the Pluronic copolymer. Bilayers are observed for Pluronic with small hydrophilic (PEO) chain lengths such as L81 [(PEO)2(PPO)40(PEO)2] and L121 [(PEO)4(PPO)60(PEO)4]; bilayer and vesicle coexistence is observed for P85 [(PEO)26(PPO)39.5(PEO)26] and F87 [(PEO)61.1(PPO)39.7(PEO)61.1]; and stable vesicles are observed for F88 [(PEO)103.5(PPO)39.2(PEO)103.5], F127 [(PEO)100(PPO)65(PEO)100], and F108 [(PEO)132.6(PPO)50.3(PEO)132.6]. The micromechanical properties of Pluronic-modified EggPC vesicles were studied by analyzing AFM approaching force curve. The bending modulus (k(c)) of the Pluronic-modified EggPC vesicles increased several-fold compared with that of the pure EggPC vesicles. The significant difference is due to the enhanced rigidity of the EggPC vesicles as a result of the incorporation of PPO molecules and PEO chains. Based on the analysis of onset point by AFM and diameters of vesicles by light scattering, it was concluded that the favorable model to describe the polymer-bilayer interaction is the membrane-spanning model.     

Effect of Pluronic F127 on the pore structure of macrocellular biodegradable polylactide foams

Thermally induced phase separation technique was utilized to fabricate biodegradable poly(l ‐lactic acid) (PLLA) macrocellular foams which were capable of being applied in tissue engineering. The block copolymer Pluronic F127 composed of (polyethyleneoxide)‐(polypropyleneoxide)‐(polyethyleneoxide) [(PEO)‐(PPO)‐(PEO)] was used as a porogen. Water/dioxane mixtures with different volume ratios were used as solvents. The addition of Pluronic F127 could induce an appearance of large pores (50–200 μm) besides small pores (10–20 μm) or a change from a solid–liquid phase separation to a liquid–liquid phase separation. The role of Pluronic F127 depends on the water/dioxane ratios in the PLLA/dioxane/water system. The X‐ray diffraction patterns and porosity measurement results showed that Pluronic F127 was crystallized and existed on the pore wall. The effect of Pluronic F127 on changing pore structure is attributed to the occurrence of the interaction of the lipophilic PPO blocks in Pluronic F127 with PLLA clews, consequently, this results in PLLA aggregation and early phase separation on cooling. Copyright © 2004 John Wiley & Sons, Ltd.     

Effects of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers on structure and stability of liposomal dioleoylphosphatidylethanolamine

The effects caused by poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO; Pluronic) copolymers on the structure and stability of dioleoylphosphatidylethanolamine (DOPE) liposomes were studied by means of turbidity, leakage, and cryo-transmission electron microscopy investigations. The results show that by inclusion of Pluronics in the DOPE dispersion it is possible to stabilize the lamellar Lalpha phase and to produce liposomes that are stable and nonleaky at low pH (pH 5). The stabilizing capacity was observed to depend critically on the molecular composition of the Pluronics. Block copolymers with comparably long PPO and PEO segment lengths, such as F127 and F108, most effectively protected DOPE liposomes prepared at high pH from aggregation and subsequent structural rearrangements induced by acidification. A sufficiently long PPO block was found to be the most decisive parameter in order to obtain adequate coverage of the liposome surface at low Pluronic concentrations. Upon increasing the copolymer concentration, however, Pluronics with comparably short PPO and PEO segment lengths, such as F87 and P85, could also be used to stabilize the DOPE liposomes. Essentially the same trends were observed when the Pluronics were added to preformed DOPE liposomes instead of being included in the preparation mixture. In this case the least effective copolymers failed, however, to completely prevent the DOPE liposomes from releasing encapsulated hydrophilic markers.     

Phase behavior and local dynamics of concentrated triblock copolymer micelles

We report a neutron-scattering study to characterize the ordering and local dynamics of spherical micelles formed by the triblock copolymer polyethylene oxide (PEO)--polypropylene oxide (PPO)--polyethylene oxide (Pluronic) in aqueous solution. The study focuses on two Pluronic species, F68 and F108, that have the same weight fraction of PEO but that differ in chain length by approximately a factor of 2. At sufficiently high concentration, both species undergo a sequence of phase changes with increasing temperature from dissolved chains to micelles with liquid-like order to a cubic crystal phase and finally back to a micelle liquid phase. A comparison of the phase diagrams constructed from small-angle neutron scattering indicates that crystallization is suppressed for shorter chain micelles due to fluctuation effects. The intermediate scattering function I(Q,t)I(Q,0) determined by neutron spin echo displays a line shape with two distinct relaxations. Comparisons between I(Q,t)I(Q,0) for fully hydrogenated F68 chains in D2O and for F68 with deuterated PEO blocks reveal that the slower relaxation corresponds to Rouse modes of the PPO segments in the concentrated micelle cores. The faster relaxation is identified with longitudinal diffusive modes in the PEO corona characteristic of a polymer brush.     

Thermodynamics of temperature-sensitive polyether-modified poly(acrylic acid) microgels

The temperature-induced structural changes and thermodynamics of ionic microgels based on poly(acrylic acid) (PAA) networks bonded with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) (Pluronic) copolymers have been studied by small-angle neutron scattering (SANS), ultra-small-angle neutron scattering (USANS), differential scanning calorimetry (DSC), and equilibrium swelling techniques. Aggregation within microgels based on PAA and either the hydrophobic Pluronic L92 (average composition, EO8PO52EO8; PPO content, 80%) or the hydrophilic Pluronic F127 (average composition, EO99PO67EO99; PPO content, 30%) was studied and compared to that in the solutions of the parent Pluronic. The neutron scattering results indicate the formation of micelle-like aggregates within the F127-based microgel particles, while the L92-based microgels formed fractal structures of dense nanoparticles. The microgels exhibit thermodynamically favorable volume phase transitions within certain temperature ranges due to reversible aggregation of the PPO chains, which occurs because of hydrophobic associations. The values of the apparent standard enthalpy of aggregation in the microgel suspensions indicate aggregation of hydrophobic clusters that are more hydrophobic than the un-cross-linked PPO chains in the Pluronic. Differences in the PPO content in Pluronics L92 and F127 result in a higher hydrophobicity of the resulting L92-PAA-EGDMAmicrogels and a larger presence of hydrophobic, densely cross-linked clusters that aggregate into supramolecular structures rather than micelle-like aggregates such as those formed in the F127-PAA-EGDMA microgels.     

pluronics和卵磷脂混合载药乳化膜的稳定性

单滴法;pluronics;卵磷脂;混合界面吸附膜;乳状液稳定性     

Pluronic microemulsions as nanoreservoirs for extraction of bupivacaine from normal saline

We hypothesized that custom-designed microemulsions would effectively scavenge compounds from bulk media. Pluronic-based oil-in-water microemulsions were synthesized that efficiently reduced the free concentration of the local anesthetic bupivacaine in 0.9% NaCl. Both the molecular nature and concentration of the constituents in the microemulsions significantly affected extraction efficiencies. Pluronic F127-based microemulsions extracted bupivacaine more efficiently than microemulsions synthesized using other Pluronic surfactants (L44, L62, L64, F77, F87, F88, P104). Extraction was markedly increased by addition of fatty acid sodium salts due to greater oil/water interface area, increased columbic interaction between bupivacaine and fatty acids sodium salt, and greater surface activity. These data suggest that oil-in-water microemulsions may be an effective agent to treat cardiotoxicity caused by bupivacaine or other lipophilic drugs.     

Effect of pharmaceuticals on thermoreversible gelation of PEO-PPO-PEO copolymers

Pluronic F127, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), has generated considerable interest as a drug delivery vehicle due to its ability to gel at physiological temperatures. This work examines the gelation behavior of Pluronic F127 in the presence of a series of hydrophobic pharmaceuticals, to determine whether there is any correlation between gelation and physicochemical parameters of drug solutes. The study includes the local anesthetics dibucaine, lidocaine, and tetracaine; the pharmaceutical additives methyl paraben, ethyl paraben, and propyl paraben; the anti-cancer agents paclitaxel and baccatin III; and the anti-inflammatory agent sulindac. The results indicate that the presence of local anesthetics and pharmaceutical additives allows F127 solutions to form gels at lower copolymer concentrations; local anesthetics and pharmaceutical additives also shift gelation down to a lower gelation temperature. This behavior is strongly dependent on drug solubility; poorly soluble drugs (paclitaxel, baccatin III, sulindac) do not change the lower gelation temperature or minimum F127 concentration for gelation. An equation relating the decrease in gelation temperature to drug solubility is presented, and the equation fits the data well. The results have significant positive implications on the toxicity and economic issues related to use of Pluronic F127 in drug delivery.     

Effect of Laponite and a nonionic polymer on the absorption character of cationic dye solutions

The effect of Laponite and an amphiphilic triblock copolymer of poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-poly(ethylene oxide) (PEO) (PEO(99)-PPO(65)-PEO(99), and labeled F127) on the absorption character of two cationic dyes, methylene blue and toluidine blue O, was studied and interpreted in terms of the changing state of aggregation of the dye molecules. The combined effect of the polymer and Laponite on dye absorption was significantly different from their individual influences. Specifically, the presence of Laponite resulted in an increase in monomer population by dispersing the dye on the silicate surface. The presence of F127 also resulted in an increase in the dye monomer population, although to a smaller extent. The combined effect of the polymer and Laponite was an increase in the dimer or aggregate populations attributed to the competition of F127 with the dye molecules for the silicate surface.     

Temperature,concentration and salt effect on F68 tri-block copolymer in aqueous solution: Rheological study

The rheology of the aqueous solution of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO?PPO?PEO) triblock copolymer, Pluronic F68 in the presence of KF was studied in the temperature range from 15 to 60°C. The variation of the shear stress according to the shear rate shows that independently from the temperature and concentration, the F68 solutions exhibit a Newtonian behavior. The results show that the Critical Micelle Temperature of Pluronic F68 in a KF aqueous solution decreases with the increase in the salt concentration.     

Controlled synthesis and association behavior of graft Pluronic in aqueous solutions

Poly(vinyl pyrrolidone) (PVP) was grafted onto Pluronic F127 (PEO-PPO-PEO) to produce novel amphiphilic PVP-g-F127 graft copolymers. A controlled synthesis method was used to graft PVP onto different parts of F127. Two types of graft polymers were obtained: one has PVP grafted onto the PEO part of F127 and the other has PVP grafted onto the PPO part of F127. The association behavior of the two modified polymers was examined using differential scanning calorimetry, surface tension measurements, and dynamic light scattering.     

The Effects of Salts and Ionic Surfactants on the Micellar Structure of Tri‐Block Copolymer PEO‐PPO‐PEO in Aqueous Solution

The micelles of two poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) (PEO‐PPO‐PEO) block copolymers, P123 and F127 (same mol wt of PPO but different % PEO) in aqueous solution in the absence and presence of salts as well as ionic surfactants were mainly examined by dynamic light scattering (DLS). The study is further supported by cloud point and viscosity measurements. The change in cloud point (CP), as well as the size of micelles in aqueous solution in presence of salts obeys the Hofmeister lyotropic series. Addition of both cationic cetylpyridinium chloride (CPC) and anionic sodium dodecylsulfate (SDS) surfactants in the aqueous solution of P123 show initial decrease of micellar size from 20 nm to nearly 7 nm and then increasing with a double relaxation mode, further in the presence of NaCl this double relaxation mode vanishes. The effect of surfactant on F127, which has much bigger hydrophilic part is different than P123 and have no double relaxation. The relaxation time distributions is obtained using the Laplace inversion routine REPES. Two relaxation modes for P123 are explained on the bases of Pluronic rich mixed micelles containing ionic surfactants and the other smaller, predominantly surfactant rich micelles domains.     

Continuous synthesis of CdSe(x)Te(1-x) nanocrystals: chemical composition gradient and single-step capping

Thermosensitive poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, Pluronic F68, containing a hydrophobic unit, oligo-(lactic acid)(oligo-LA) or oligo-caprolactone (oligo-CL), 2-META and RGD as side groups was successfully synthesized and characterized by (1)H NMR, FTIR, and elemental analysis. Their aqueous solution displayed special gel-sol-gel phase transition behavior with increasing temperature from 10 to 70°C, when the polymer concentration was above critical micelle concentration (CMC). The gel-sol phase diagram was investigated using tube inversion method, rheological measurement, and dynamic light scattering. Based on these results, the gelation properties of modified F68 were affected by several factors such as the composition of the substituents, chain length of oligo L-LA or oligo ε-CL, and the concentration of the polymer solutions. The unique phase transition behavior with temperature was observed by modified F68 triblock copolymer, composed of the PPO blocks core and the PEO blocks shell in aqueous solution. This phenomenon was elucidated using (1)H NMR data; the alteration of hydrophobic interaction and chain mobility led to the formation of transparent gel, coexistence of gel-sol, and opaque gel. These hydrogels may be useful in drug delivery and tissue engineering.     

二元Pluronic嵌段共聚物相互作用

用I2探针增溶分光光度法考察二元Pluronic两亲嵌段共聚物在水溶液中的胶束化行为,实验结果表明,对于分子PPO嵌段长度相近的P94/L92和F108/L92二元混合体系,这些分子在全部浓度比例范围内都发生相互作用,生成了混合胶束,由于这些分子的PEO嵌段长度不等,随着具有较短PEO嵌段的L92分子加入,P94/L92和F108/L92混合胶束外壳的EO基团数减少导致水化度降低。对于分子PPO嵌段长度不等的P94/L64二元混合体系,当溶液体当中L64的质量分数wL64<0.4时,由于P94/L64混合预胶束的形成,使P94分子在较高浓度时才生成单组分胶束,当wL64>0.4后,溶液中生成了P94/L64混合胶束,温度升高促进了胶束化行为。     

Molecular dynamics simulation study of solvent effects on conformation and dynamics of polyethylene oxide and polypropylene oxide chains in water and in common organic solvents

In this paper, the conformation and dynamics properties of polyethylene oxide (PEO) and polypropylene oxide (PPO) polymer chains at 298 K have been studied in the melt and at infinite dilution condition in water, methanol, chloroform, carbon tetrachloride, and n-heptane using molecular dynamics simulations. The calculated density of PEO melt with chain lengths of n = 2, 3, 4, 5 and, for PPO, n = 7 are in good agreement with the available experimental data. The conformational properties of PEO and PPO show an increasing gauche preference for the O-C-C-O dihedral in the following order water>methanol>chloroform>carbon tetrachloride = n-heptane. On the contrary, the preference for trans conformation has a maximum in carbon tetrachloride and n-heptane followed in the order by chloroform, methanol, and water. The PEO conformational preferences are in qualitative agreement with results of NMR studies. PEO chains formed different types of hydrogen bonds with polar solvent molecules. In particular, the occurrence of bifurcated hydrogen bonding in chloroform was also observed. Radii of gyration of PEO chains of length larger than n = 9 monomers showed a good agreement with light scattering data in water and in methanol. For the shorter chains the observed deviations are probably due to the enhanced hydrophobic effects caused by the terminal methyl groups. For PEO the fitting of end-to-end distance distributions with the semi-flexible chain model at 298 K provided persistence lengths of 0.375 and 0.387 nm in water and methanol, respectively. Finally, the radius of gyration of Pluronic P85 turned out to be 2.25 ± 0.4 nm at 293 K in water in agreement with experimental data.     

Tuning of the Temperature Window for Unit‐Cell and Pore‐Size Enlargement in Face‐Centered‐Cubic Large‐Mesopore Silicas Templated by Swollen Block Copolymer Micelles

The unit‐cell size and pore diameter as functions of temperature are investigated in the syntheses of FDU‐12 silicas with face‐centered cubic structure templated by Pluronic (PEO‐PPO‐PEO) block copolymer micelles swollen by toluene. The temperature range in which the unit‐cell size and pore size strongly increase as temperature decreases is correlated with the critical micelle temperature (CMT) of the surfactant. While Pluronic F127 affords a wide range of unit‐cell parameters (28–51 nm) and pore diameters (16–32 nm), it renders moderately enlarged pore sizes at 25 °C. The use of Pluronic F108 with higher CMT affords FDU‐12 with very large unit‐cell size (～49 nm) and large pore diameter (27 nm) at 23 °C. Large unit‐cell size (40–41 nm) and pore size (22 nm) were obtained even at 25 °C. The application of Pluronics F87 and F88 with much smaller molecular weights and higher CMTs also allows one to synthesize FDU‐12 with quite large unit‐cell parameters and pore sizes at room temperature. The present work demonstrates that one can judiciously select Pluronic surfactants with appropriate CMT to shift the temperature range in which the pore diameter is readily tunable.     

Salt‐Induced Micellization of Pluronic F88 in Water

The effect of potassium chloride on the micellization of a poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) (PEO‐PPO‐PEO) triblock copolymer (Pluronic F88: EO₁₀₃PO₃₉EO₁₀₃.) in water was studied by fluorescence, FTIR, ¹H NMR, dynamic light scattering, and dye solubilization. The critical micellization temperature (CMT) values of the copolymer decreased with an increase of KCl concentration while micellar core gets progressively dehydrated. The results reveal the leading role of salt‐water interaction in promoting the micellization of PEO‐PPO‐PEO copolymer by the addition of salt. No significant micellar growth was seen even at temperatures close to cloud point.     

Two Gel States of a PEO‐PPO‐PEO Triblock Copolymer Formed by Different Mechanisms

Two gel states of a PEO‐PPO‐PEO (Pluronic P103) triblock copolymer in water are investigated using small‐angle X‐ray scattering, rheology and differential scanning calorimetry. The first gel state turns out to be the hexagonal microphase while the second gel state, showing turbidity change with four distinct regions, is somewhat disrupted. The second gel is moreover not thermoreversible as evidenced by rheology. Based upon the present study, two different gelation mechanisms for aqueous PEO‐PPO‐PEO solutions are proposed.     

Aqueous two-phase systems containing self-associating block copolymers. Partitioning of hydrophilic and hydrophobic biomolecules.

A series of proteins and one membrane-bound peptide have been partitioned in aqueous two-phase systems consisting of micelle-forming block copolymers from the family of Pluronic block copolymers as one polymer component and dextran T500 as the other component. The Pluronic molecule is a triblock copolymer of the type PEO-PPO-PEO, where PEO and PPO are poly(ethylene oxide) and poly(propylene oxide), respectively. Two different Pluronic copolymers were used, P105 and F68, and the phase diagrams were determined at 30 degrees C for these polymer systems. Since the temperature is an important parameter in Pluronic systems (the block copolymers form micellar-like aggregates at higher temperatures) the partitioning experiments were performed at 5 and 30 degrees C, to explore the effect of temperature-triggered micellization on the partitioning behaviour. The temperatures correspond to the unimeric (single Pluronic chain) and the micellar states of the P105 polymer at the concentrations used. The degree of micellization in the F68 system was lower than that in the P105 system, as revealed by the phase behaviour. A membrane-bound peptide, gramicidin D, and five different proteins were partitioned in the above systems. The proteins were lysozyme, bovine serum albumin, cytochrome c, bacteriorhodopsin and the engineered B domain of staphylococcal protein A, named Z. The Z domain was modified with tryptophan-rich peptide chains in the C-terminal end. It was found that effects of salt dominated over the temperature effect for the water-soluble proteins lysozyme, bovine serum albumin and cytochrome c. A strong temperature effect was observed in the partitioning of the integral membrane protein bacteriorhodopsin, where partitioning towards the more hydrophobic Pluronic phase was higher at 30 degrees C than at 5 degrees C. The membrane-bound peptide gramicidin D partitioned exclusively to the Pluronic phase at both temperatures. The following trends were observed in the partitioning of the Z protein. (i) At the higher temperature, insertion of tryptophan-rich peptides increased the partitioning to the Pluronic phase. (ii) At the lower temperature, lower values of K were observed for ZT2 than for ZT1.