Showing papers on "Poloxamer published in 2003"

NMR Study of the Association of Propofol with Nonionic Surfactants

Abstract: The general anesthetic 2,6-diisopropylphenol (propofol) is very poorly soluble in water and is normally administered in the form of an emulsion We demonstrated that several commercially available nonionic surfactants (Tween 80, Cremophor EL, Poloxamer 188, Poloxamer 407, Solutol HS15, and Vitamin E TPGS)render propofol soluble with a specific solubilization capacity of at least 01 g/g The room-temperature stability of the solutions appeared to be limited only by the chemical stability of the compounds involved Theassociation between propofolandthe surfactantswasinvestigated by various NMR approaches, including measurements of diffusion coefficients, 1H longitudinal relaxation times, and the magnitude of intermolecular nuclear Overhauser effects The results were consistent with the micellar solubilization mechanism of propofol by the surfactants (unimer solubilization in the case of Poloxamer 188) The 1H longitudinal relaxation and diffusion behavior of propofol were monoexponential in each case Solubilization caused a considerable shortening of propofol’s proton T1’s The values of the diffusion coefficient of propofol were several percent higher than those of surfactants This was explained by the partitioning of propofol between swollen micelles and the aqueous solution Diffusion measurements also revealed the presence of a rapidly diffusing ethylene oxide population in surfactant solutions, which is consistent with free poly(ethylene oxide) (PEO) known to be present in commercially produced surfactants The free PEO blocks exhibited molecular association with the extramicellar propofol

Plasma protein adsorption of Tween 80- and poloxamer 188-stabilized solid lipid nanoparticles.

Abstract: The plasma proteins adsorbing onto intravenously injected carriers are considered to be crucial factors determining the organ distribution. Plasma protein adsorption patterns were analyzed on solid lipid nanoparticles (SLN) stabilized with Tween 80 or stabilized with poloxamer 188. The binding patterns were determined by applying two different sample preparation methods, i.e. removal of the SLN from the plasma by (a) centrifugation and (b) gel filtration to assess, if the separation method has an effect on the patterns obtained. The Tween 80-modified SLN adsorbed the major plasma proteins known from particles with blood-brain barrier specificity. Poloxamer 188-surface modified SLN adsorbed the proteins known from model particles that exhibit prolonged circulation time in the blood. It is concluded that the biodegradable SLN stabilized with Tween 80 can potentially be used as drug carriers to the blood-brain barrier having a relatively long residence time in the blood stream. For the poloxamer 188-stabilized SLN a relatively long resistance time in the blood is predicted leading to potential accumulation in the bone marrow when looking at the distinct CII/CIII adsorption.

Comparative Study of Poloxamer Insertion into Lipid Monolayers

Abstract: Surface pressure versus area isotherms have been coupled with fluorescence microscopy to compare the insertion preferences of a series of triblock copolymers of the form poly(ethylene oxide)−poly(p...

Development of in situ gelling and mucoadhesive mebeverine hydrochloride solution for rectal administration

Abstract: ,An investigation of the ethanolic extract of the pods of Albizzia lebbeck (L.) Benth. afforded a Mebeverine hydrochloride (MbHCl) is well known to suffer from extensive first pass effect. In an attempt to improve its bioavailability and possibility restrict its absorption to only the lower rectum, rectal solution with gelation at temperature range of 30-37C o . Mixtures of poloxamer 407 (P407) and poloxamer 188 (P188) were used to confer the temperature-sensitive gelation property. To modulate the gel strength and the mucoadhesive force of MbHCl poloxamer rectal solution, mucoadhesive polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose (HEC), methyl cellulose (MC) and polyvinylpyrrolidone K-25 (PVP K-25) were investigated. Incorporation of 10% w/w MbHCl in the rectal solution increased the gelation temperature of the poloxamers mixtures, while the addition of the mucoadhesive polymers had a reverse effect. On the other hand, these polymers reinforced the gel strength and the mucoadhesive force of the prepared solutions. The effect was most pronounced with MC. Increasing the concentration of cellulosic bioadhesive polymers retarded the release of MbHCl from the poloxamer solutions to different extents, and it was possible to sustain the drug effect over a period of 8 hours. PVP K-25 had no effect on drug release. Pretreatment of guinea pigs with MbHCl rectal solution [P407/ P188/ MC/ MbHCl (23/ 7/ 1.5/ 10% w/w)], having satisfactory gel strength, mucoadhesive properties and acceptable sustained release profile with zero order release kinetics, showed a significant extended spasmolytic effect to spasmogens-induced contractions on guinea pig ileum and did not cause any histological damage to the rectal tissues.

Evaluation of sucrose esters as alternative surfactants in microencapsulation of proteins by the solvent evaporation method.

Abstract: Sucrose esters (SE) are surfactants with potential pharmaceutical applications because of their low toxicity, biocompatibility, and excellent biodegradability. The objective of the study was to investigate SE as alternative surfactants in stabilizing emulsions for the preparation of protein-loaded microparticles. To achieve this goal, using bovine serum albumin as model protein and 75/25 poly(d,1-lactide-co-glycolide) as polymer carrier, we have investigated the influence of the following formulation variables on particle characteristics: (1) SE concentration from 0.01% to 1% (wt/vol), (2) hydrophile-lipophile balance (HLB) value of SE from 6 to 15, and (3) the nature of emulsion stabilizer. The formulations were characterized using ATR-FTIR spectroscopy, bicinchoninic acid protein assay, optical microscopy and SDS-PAGE. Results showed that at 0.05% (wt/vol) surfactant concentration, SE with HLB of 6 to 15 provided discrete and spherical microparticles with the highest encapsulation efficiency compared with controls polyvinyl alcohol (PVA) and poloxamer 188. These results may be explained by the difference in critical micelle concentration, diffusion, and partition coefficient among the tested surfactants. HLB values were consistent with SE spectral data. The protein molecular weight was preserved after the encapsulation process. The effective SE concentration was far less (20-to 200-fold) than that is usually required for PVA in microencapsulation of proteins. However, the encapsulation efficiency was relatively lower (∼13.5%). These preliminary results suggest that it may be desirable to optimize such formulations in vitro and in vivo for SE to be eventually used as altermative surfactants in the development of microparticulate systems for parenteral delivery of protein and gene medicines.

Block Copolymers of Methyl Vinyl Ether and Isobutyl Vinyl Ether With Thermo‐Adjustable Amphiphilic Properties

Abstract: Full Paper: The thermo-adjustable hydrophilic/hydrophobic properties of AB, ABA and BAB block copolymers in which A is poly(methyl vinyl ether) (PMVE) and B is poly(isobutyl vinyl ether) (PIBVE) have been investigated. The block copolymers were prepared by "living" cationic polymerization using sequential addition of monomers. The polymerizations were carried out with the system acetal/trumethylsilyl iodide as initiator and ZnI 2 as activator. The initiating system based on diethoxyethane leads to AB block copolymers whereas the initiating system based on tetramethoxypropane leads to ABA or BAB triblock copolymers. Well-defined block copolymers of different composition with controlled molecular weights up to approx. 10 000 have been prepared. When IBVE is added to living PMVE, PIBVE-blocks form only in the presence of an additional amount of ZnI 2 which is attributed to the fact that part of the ZnI 2 is inactive because of complex formation with PMVE. At room temperature, the combination of hydrophilic (PMVE) and hydrophobic (PIBVE) segments provides the copolymers with surfactant properties. Above the lower critical solution temperature (LCST) of PMVE, situated around 36°C, the PMVE-blocks become hydrophobic and the amphiphilic nature of the block copolymers is lost. The corresponding changes in hydrophilic/hydrophobic balance have been evaluated by investigation of the emulsifying properties of the blcok copolymers for water/decane mixtures as a function of the temperature. Below the LCST, the block copolymers have emulsifying properties similar to or better than those of the commercial PEO-PPO block copolymers (Pluronic ®). Either oil-in-water or water-in-oil emulsions can be obtained, depending on the polymer architecture and the water/decane volume ratio. The emulsifying properties are strongly reducted or completely lost above 40°C. Emulsions obtained with a PMVE 3 6 -b-PIBVE 5 4 block copolymer for a water/decane (v/v) ratio of 85/15 remained stable for more than six months.

Effect of Pluronic-block copolymers on the reduction of serum-mediated inhibition of gene transfer of polyethyleneimine-DNA complexes.

Abstract: Serum stability of non-viral vectors is a crucial factor for successful in vivo gene delivery. Pluronic-block copolymers consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks were tested to prevent the reduction of serum-mediated inhibition of gene transfer of polyethyleneimine (PEI)-DNA complexes in NIH/3T3 cells. The order of hydrophilic-lipophilic balance (HLB) of six different types of Pluronics used in this study was F68>F127>P105>P94>L122>L61. Transfection activities of NIH/3T3 cells with PEI-DNA complexes containing Pluronics with higher HLB showed marked improvement of gene-expression levels in serum media from 10 to 50% fetal bovine serum compared with PEI-DNA complexes alone. Also, higher concentrations (1 and 3%) of Pluronics with higher HLB in the PEI/DNA dispersion provided a stronger steric hindrance in resisting serum components than those obtained in a lower concentration (0.1%). These results suggested that non-viral vectors incorporated with higher HLB of Pluronics may be used as potential vehicles for in vivo delivery of DNA.

Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose

Abstract: A polymeric film composed of Carbopol, Poloxamer and hydroxypropyl methylcellulose was prepared to develop a buccal patch and the effects of composition of the film on adhesion time, swelling ratio, and dissolution of the film were studied. The effects of plasticizers or penetration enhancers on the release of triamcinolone acetonide (TAA) were also studied. The hydrogen bonding between Carbopol and Poloxamer played important role in reducing swelling ratio and dissolution rate of polymer film and increasing adhesion time. The swelling ratio of the composite film was significantly reduced and the adhesion time was increased when compared with Carbopol film. As the ratio of Poloxamer to hydroxypropyl methylcellulose increased from 0/66 to 33/33, the release rate of TAA decreased. However, no further significant decrease of release rate was observed beyond the ratio of 33/33. The release rate of TAA in the polymeric film containing polyethylene glycol 400, a plasticizer, showed the highest release rate followed by triethyl citrate, and castor oil. The release rate of TAA from the polymeric film containing permeation enhancers was slower than that from the control without enhancers. Therefore, these observations indicated that a preparation of a buccal patch is feasible with the polymeric film composed of Cabopol, Poloxamer and hydropropyl methylcellulose.

Formulation of Benzoporphyrin Derivatives in Pluronics

Abstract: This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.

Diffusion and Release of Solutes in Pluronic-g-poly(acrylic acid) Hydrogels

Abstract: Pluronic−PAA, a thermogelling copolymer composed of side chains of poly(acrylic acid) (PAA) grafted onto a backbone of Pluronic copolymer, is of interest as a vehicle for the controlled release of compounds. The diffusion of various electrochemically active solutes (ferricyanide, the redox protein cytochrome c, and a range of ferrocene derivatives) with varying sizes and hydrophobicities has been examined in solutions and hydrogels of Pluronic−PAA. Release of the solutes from the hydrogel into aqueous media has also been examined. Small hydrophilic molecules diffused freely through the hydrogel, but diffusion of more hydrophobic species was retarded due to their association with hydrophobic micellar aggregates formed on gelation of Pluronic−PAA. The rate of release of solutes from the hydrogel into aqueous media also decreased with increasing hydrophobicity. Constant-rate release was observed over a considerable time period for hydrophobic materials. Cytochrome c exhibited reduced diffusion coefficients a...

In vitro and in vivo study of lens refilling with poloxamer hydrogel

Abstract: Aim: To evaluate the compatibility of poloxamer hydrogel as a material for an injectable intraocular lens, in vivo and in vitro. Methods: The appropriate concentration of poloxamer hydrogel was determined for injection by examining the transparency and gelling temperature of this material, assessing the lens capsule refilling technique, and studying the postoperative findings in a rabbit model. Results: Poloxamer hydrogel showed excellent transparency and 25% was identified as an appropriate concentration for the lens refilling material. The authors developed a technique for injecting the material in vivo and obtained excellent short term results. Conclusions: Poloxamer hydrogel was identified as an appropriate material for direct lens refilling, and the developed injection technique produced excellent short term results.

Solute and solvent effects on the thermorheological properties of poly(oxyethylene)–poly(oxypropylene) block copolymers: Implications for pharmaceutical dosage form design

Abstract: Despite their widespread use as platforms for topical drug delivery systems, there is a relative lack of information concerning the thermorheological and viscoelastic properties of poloxamer systems and the effects of formulation components on these properties. To address this deficit, we examined the effects of the poloxamer concentration (25 and 35% w/w), molecular weight blend (poloxamer 407 and poloxamer 188), cosolvents (ethanol, propylene glycol, and glycerol), and presence of inorganic and organic electrolytes (sodium chloride and tetracaine hydrochloride, respectively) on these properties. The rheological properties were examined with a rheometer (4-cm-diameter, stainless steel, parallel-plate geometry) in either thermal sweep (0.5 Hz) or frequency sweep (0.01–1.0 Hz and 37°C) modes. Increasing the poloxamer concentration increased the elasticity [i.e., increased the storage modulus (G′) and reduced the loss tangent (tan δ)] and reduced the sol–gel transition temperature (Tm) of all the formulations. Decreasing the ratio (407:188) increased Tm and reduced the elasticity of all the formulations. Increasing the concentration of ethanol, propylene glycol, or glycerol in the solvent reduced Tm. The presence of ethanol reduced G′ and increased tan δ in a concentration-dependent fashion, whereas the viscoelastic properties of the poloxamers were more tolerant of glycerol (in particular) and propylene glycol. The elasticity of the formulations containing up to 10% glycerol and 5% propylene glycol was increased with respect to their aqueous counterparts. The presence of sodium chloride reduced Tm and, at lower concentrations (1 and 3%), increased G′ and reduced tan δ for aqueous poloxamer systems. Conversely, the addition of a model therapeutic agent, tetracaine hydrochloride (5 and 7% w/w), significantly increased Tm and altered the viscoelastic character of the poloxamer system, notably reducing G′ and increasing the loss modulus and tan δ. Alterations in the viscoelastic and thermorheological properties of aqueous poloxamer systems will have implications for their clinical performance. This study, therefore, has highlighted the need for the rational selection of components in the formulation of poloxamer systems as platforms for topical drug delivery. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1016–1026, 2003

Improved Solubility and In Vitro Dissolution of Ibuprofen from Poloxamer Gel Using Eutectic Mixture with Menthol

Abstract: To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.

Influence of process parameters of high-pressure emulsification method on the properties of pilocarpine-loaded nanoparticles

Abstract: Poly(lactide-co-glycolide) nanoparticles loaded with pilocarpine hydrochloride were prepared by the high-pressure emulsification-solvent evaporation method. The nanoparticles were produced using polyvinylalcohol (PVA), carbomer (Carbopol 980) or poloxamer (Lutrol F-68) as stabilizers during emulsification. The influence of pressure and number of cycles on the nanoparticle properties was investigated. For comparison, nanoparicles without high-pressure treatment of the emulsion were made. The nanoparticle size, drug loading and release properties depended strongly on the homogenization pressure and number of cycles applied. Nanoparticles obtained without high pressure homogenization showed larger size and high values of polydispersity index, especially when carbopol and poloxamer were used as emulsifiers. Drug loading and encapsulation efficiency of all samples also decreased with pressure. The low drug loading could be due to two reasons. First, the high pressure promoted drug diffusion out of protoparticles during emulsification either by size reduction or shear forces. Secondly, the characteristics of the outer water phase of the emulsion also influenced the nanoparticle drug loading. This was proven by the different drug loadings measured when nanoparticles were made with PVA, carbopol or poloxamer at equal pressures applied. The main factor influencing the release properties of nanoparticles was the pressure used during emulsification. Faster drug release was observed from nanoparticles obtained after high-pressure emulsification compared to those prepared without homogenization of the emulsion.

Fluorescence spectroscopy studies on micellization of poloxamer 407 solution.

Abstract: It has been reported that at low temperature region, poloxamers existed as a monomer. Upon warming, an equilibrium between unimers and micelles was established, and finally micelle aggregates were formed at higher temperature. In this study, the fluorescence spectroscopy was used to study the micelle formation of the poloxamer 407 in aqueous solution. The excitation and emission spectra of pyrene, a fluorescence probe, were measured as a function of the concentration of poloxamer 407 and temperature. A blue shift in the emission spectrum and a red shift in the excitation spectrum were observed as pyrene transferred from an aqueous to a hydrophobic micellar environment. From the l1/I3 and I339/I333 results, critical micelle concentration (cmc) and critical micelle temperature (cmt) were determined. Also, from the fluorescence spectra of the probe molecules such as 8-anilino-1-naphthalene sulfonic acid and 1-pyrenecar-boxaldehyde, the blue shift of the λmax was observed. These results suggest a decrease in the polarity of the microenvironment around probe because of micelle formation. The poloxamer 407 above cmc strongly complexed with hydrophobic fluorescent probes and the binding constant of complex increased with increasing the hydrophobicity of the probe.

Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.

Abstract: Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

Preparation of a novel poloxamer hydrogel

Abstract: Poloxamer hydrogels were prepared by photopolymerization from poloxamer macromer, which was synthesized by reaction of poloxamer 407 with acryloyl chloride. The synthesis of poloxamer macromer was confirmed using NMR and FTIR spectrometry. The gelation behavior and crystalline structure of poloxamer macromer was similar to those of poloxamer 407 itself; however, the amorphous scattering of poloxamer macromer was higher than that of poloxamer itself. Differential scanning calorimetric analysis showed that the melting temperature and enthalpy of poloxamer hydrogel were also lower than those of poloxamer itself. The compressive modulus of poloxamer hydrogels were similar (92.6–101.7 kPa), regardless of the concentration of poloxamer macromer. Equilibrium water uptake of poloxamer hydrogels decreased with an increase of concentration of poloxamer macromer. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2670–2676, 2003

Thermoplastic hydrogel based on pentablock copolymer consisting of poly(γ-benzyl L-glutamate) and poloxamer

Abstract: A thermoplastic hydrogel based on a pentablock copolymer composed of poly(γ-benzyl L-glutamate) (PBLG) and poloxamer was synthesized by polymerization of BLG N-carboxyanhydride, which was initiated by diamine-terminated groups located at the ends of poly(ethylene oxide) (PEO) chains of the poloxamer, to attain a new pH- and temperature-sensitive hydrogel for drug delivery systems. Circular dichroism measurements in solution and IR measurements in the solid state revealed that the polypeptide block existed in the α-helical conformation, as in the PBLG homopolymer. The intensity of the wide-angle X-ray diffraction patterns of the polymers depended on the poloxamer content in the copolymer and showed basically similar reflections to the PBLG homopolymer. The melting temperature (Tm) of the poloxamer in the copolymer was reduced with an increase of the PBLG block in comparison with the Tm of the poloxamer, which is indicative of a thermoplastic property. The water contents of the copolymers were dependent on the poloxamer content in the copolymers, for example, those for the GPG-2 (48.7 mol % poloxamer) and GPG-1 (57.5 mol % poloxamer) copolymers were 31 and 41 wt %, respectively, indicating characteristics of a polymeric hydrogel. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2649–2656, 2003

Polymerization of n-butyl cyanoacrylate in presence of surfactant: study of influence of polymerization factors on particle properties, drug loading and evaluation of its drug release kinetics

Abstract: Polybutyl cyanoacrylate nanoparticles were synthesized by emulsion polymerization in presence of nonionic surfactant (Poloxamer 188) in concentration above CMC, and were characterized by particle size analysis, transmission electron microscopy and zeta potential measurements. Effect of polymerization factors such as monomer concentration, polymerization

Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide)Block Copolymers in Bovine Serum Albumin Aqueous Solutions

Abstract: Temperaturedependent association behavior of poly(ethylene oxide)poly (propylene oxide)poly (ethylene oxide) (PEOPPOPEO) block copolymers in Bovine Serum Albumin (BSA) aqueous solution has been investigated using pyrene fluorescence spectrum. The critical micellization temperature (CMT) of Pluronics in aqueous solution is increased by the addition of BSA. It is explained by the hydrophobic interaction between BSA and PO block.

Peg-Containing Surfactants Enhance the Ultrasonic Permeabilizability of Liposomes

Abstract: The susceptibility of phosphatidylcholine liposomes to rupture by ultrasound was investigated. The liposomes were treated with (or had incorporated) a surface active dopant. The dopants studied here all contain polymers or oligomers of ethylene glycol as their hydrophilic “headgroup” component. All dopants strongly increased the ultrasonic permeabilizability of liposomes, as measured by the rate of release of a self-quenching fluorescent dye, at concentrations that caused no increase in permeability in the absence of ultrasound. The surface active dopants reached maximal effectiveness at about 1% of their critical micelle concentrations (CMCs). Using the roughly inverse relationship between CMC and membrane partition coefficient, we estimate that these maximally effective concentrations correspond approximately to the onset of headgroup contact among the surfactants in the membrane. Two surfactants, a PEG-lipid and a Pluronic triblock polymer, can be irreversibly incorporated into liposomes to give formulations that could in principle be used as drug delivery vehicles. The Pluronic polymer offers the possibility of additional temperature responsivity, owing to its highly temperaturedependent CMC.

Rheological Behavior of Poloxamer 407 Solution and Effect of Poly(ethylene glycol) on the Gelation

Abstract: 【The rheological behavior of poloxamer 407 solution as function of concentration and temperature was evaluated by rotational viscometer. The viscosity of poloxamer 407 solution was increased as the concentration of poloxamer 407 and temperature increased. At $4^{\circ}C$ , poloxamer 407 solution showed the Newtonian flow characteristics regardless of concentration. Upon increasing temperature the poloxamer solution changed to the pseudoplastic flow pattern. And at gelation temperature, rheological profiles showed the abrupt increase in viscosity. Gelation temperature was decreased as the concentration of poloxamer 407 increased, while it increased as the concentration of poly(ethylene glycol) 4000 increased. Poly(ethylene glycol) might be expected to reduce the driving force for hydrophobic interaction resulting in slow gelation. From the viscoelastic properties of poloxamer gel system, we obtained the storage and loss modulus depending on the shear stress and frequency. And the sol-gel transition temperature was also obtained from the viscoelastic properties of poloxamer 407 gel.】