Surfactant Poloxamer Research Articles

Interaction of Nonionic Block Copolymeric (Poloxamer) Surfactants with Poly (Acrylic Acid), Studied by Photon Correlation Spectroscopy

The interaction between certain hydrophilic pluronic (poloxamer) surfactants and a poly (acrylic acid) has been investigated. Both the PPO and the PEO groups of the surfactants, and the -COOH groups and aliphatic side chains of the PAA molecule, were found to be crucial in this interaction to form complexes. At pH 2 and with a low poloxamer:PAA molar ratio, maximum interaction was observed, giving rise to large-sized complexes that were unstable but possessing bioadhesive properties. At the same pH but with higher poloxamer:PAA molar ratio, the complexes became smaller in size and more stable and were used to prepare stable w/o/w emulsions. A further increase in the poloxamer:PAA molar ratio or increase in the pH causes a further decrease in particle size with eventual nonformation of complexes. Interaction and stability studies of the complexes were done using photon correlation spectroscopy. The overall interaction appears to be a combination of hydrophobic interaction and hydrogen bonding. This has given rise to a unique ratio which we have called the [oxyphobic]/[oxyphilic] ratio or OOR. The interaction was found to depend on the molar ratio between poloxamer surfactants and PPA; the [O]total/[-COOH] ratio; the size of the PPO hydrophobe, and the pH of the reaction mixture. pH measurement studies of these mixtures also gave similar results.

The effect of adsorbed poloxamer 188 and 407 surfactants on the intestinal uptake of 60-nm polystyrene particles after oral administration in the rat

The surface properties of 60-nm polystyrene particles were modified by the adsorption of poloxamer 188 and 407 surfactants, and the effect of this change on the intestinal uptake of the particles studied. In comparison to uncoated polystyrene particles, the surfactant-coated particles had an increased particle diameter, as measured by photon correlation spectrometry, and lower zeta potential. Uptake of the coated polystyrene particles by gut epithelial tissue was studied in female Sprague-Dawley rats (180 g, 9 weeks old) after 5 days oral dosing by gavage. The small and large intestine was divided into lymphoid and non-lymphoid tissue, prior to analysis for polystyrene by gel permeation chromatography and visualization of particle uptake using fluorescent microscopy. The adsorption of poloxamer surfactants onto the polystyrene particles appeared to completely inhibit particle uptake in the small intestine. Polystyrene uptake was shunted to the large intestine, with the detection in this region of approximately 3% and 1.5% of the dose of poloxamer 407 and 188 coated particles, respectively. This uptake was less than the 10% uptake across the entire GI tract (5.1% uptake in the large intestine) determined for uncoated polystyrene particles.

The effect of temperature on the surface nature of an adsorbed layer of poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) block copolymers.

To investigate the influence of the temperature at which adsorption takes place and the temperature at which the adsorbed surface is studied on the polarity of Poloxamer adsorbed to a hydrophobic surface. The implication is that changes in surface nature of adsorbed Poloxamer may subsequently be related to functionality, such as changes in opsonisation of Poloxamer coated latex in animals. The surface energies of Poloxamer surfactant have been calculated following adsorption to silanised glass plates. The adsorption to the plates was undertaken at a range of concentrations and at different controlled temperatures. The contact angles were measured using three different liquids on each surface, at a range of controlled temperatures. The surface energies were calculated using the harmonic mean and the acid-base models, via Wilhelmy plate contact angle measurements. These data were compared with previously published adsorption and hydrophobic interaction chromatography studies. The apolar surface energy term remained consistent, but the polar contribution (which was totally of the electron donor type) changed depending upon the temperature of adsorption (and to a lesser extent the temperature at which the surface energy was measured). The polar nature was most elevated at the critical micelle concentration/temperature. The data are consistent with estimates of surface hydrophobicity made using hydrophobic interaction chromatography. It is argued that the changes in surface energy, which result from the different adsorption conditions, can be expected to influence the functionality of the adsorbed coat, especially for application such as drug targeting.

Preparation of Stable Multiple W/O/W Emulsions Using Pluronic (Poloxamer):Poly(acrylic Acid) Complexes

A detailed study of the interactions between poly(acrylic acid) (PAA) and a range of hydrophilic poloxamer surfactants was undertaken. This enabled us to use the most appropriate combinations of these surfactants and PAA to prepare stable multiple w/o/w emulsions. Poly(acrylic acid) as Carbopol 907 was reacted with poloxamer surfactants in the forms of Pluronic F127, P104, P103, F68, P75, and P85 at pH 2, to form Pluronic (poloxamer): PAA complexes which were then used to prepare multiple w/o/w emulsions. Two types of Pluronic:PAA complexes were derived from these interactions with different particle sizes and varying bioadhesive properties. The stability of the complexes was determined by photon correlation spectroscopy while that of the emulsions was determined using a Malvern particle sizer, over a 28-day period. Stability of the emulsions prepared with these complexes were found to be related to the particle sizes of the Pluronic (poloxamer):PAA complexes and the type of lipophilic surfactants in the oil phases. The emulsion droplet sizes were also found to be related to the Pluronic (poloxamer):PAA complex sizes.

Enhancement of antibiotic susceptibility and suppression of Mycobacterium avium complex growth by poloxamer 331

The resistance of Mycobacterium avium complex (MAC) to antibiotics is thought to be enhanced by its outer glycolipid layer, which protects the organisms from antibiotics and host defense mechanisms. We hypothesized that surfactants which disrupt the lipid barrier might be of therapeutic value. We evaluated the ability of 10 poloxamer surfactants to inhibit the growth of MAC organisms and to potentiate antimycobacterial drug activity in broth culture using a radiometric assay. Very large, small, or hydrophilic poloxamers had little or no effect. However, certain hydrophobic poloxamers, especially P331, retarded the growth of most isolates of MAC and produced a synergistic effect with rifampin. The MIC of rifampin required to inhibit the growth of MAC was reduced from a mean of 14.6 micrograms/ml (range, 4 to > 32 micrograms/ml) to 1.4 micrograms/ml (range, < 1.125 to 4 micrograms/ml) by 1.0 mg of P331 per ml (P < 0.01). Enhancement of antibiotic susceptibility was observed with concentrations of poloxamer as low as 10 micrograms/ml. These studies suggest that P331 might be useful in increasing the effectiveness of antibiotic therapy of MAC infections.

Effects on splenic, hepatic, hematological, and growth parameters following high-dose poloxamer 407 administration to rats

The nonionic surfactant poloxamer 407, NF (PIuronic ® F-127, NF) has previously been shown to produce marked hyperlipidemia in rats at a dose of 1.5 g/kg for greater than 96 h following a single intraperitoneal (i.p.) injection (Wout et al. J. Parenter. Sci. Technol., 46 (1992) 192–200). In an effort to characterize any potential toxicity of the polymeric vehicle to various organ systems in the rat following multiple i.p. injections, a dose of 0.33 g/kg per day (10% w/w solution) or 1.0 g/kg per day (30% w/w solution) of poloxamer 407 was administered once daily for 4 consecutive days. When compared to control (non-injected) animals, rats injected with 0.33 g/kg per day of poloxamer 407 did not show a significant ( p > 0.05) increase or decrease in spleen, liver, or total body weight. A complete blood count (CBC) with a white blood cell (WBC) differential was performed on blood samples collected on day five from rats injected with poloxamer 407 at both doses. The CBC with WBC differentia] was conducted to assess any changes in the WBC count, percent lymphocytes (LY), percent monocytes (MO), percent granulocytes (GR), red blood cell (RBC) count, hemoglobin (HGB), percent hematocrit (HCT), and the mean corpuscular volume (MCV) following administration of poloxamer 407. Rats injected i.p. with a dose of 0.33 g/kgper day of poloxamer 407 for 4 days demonstrated a significant ( p < 0.05) increase in the number of MO when compared to controls. Administration of 1.0 g/kg per day of poloxamer 407 to rats for 4 days demonstrated distinct splenomegaly when compared to non-injected control animals. In addition, a significant ( p < 0.05) reduction in body weight and significant ( p < 0.05) decrease in the percent LY, RBCs, HGB, and percent HCT were noted. Lastly, a significant ( p < 0.05) increase in the number of WBCs and the percent MO was observed in this same group of rats. However, rats administered 1.0 g/kg per day of poloxamer 407 for 4 days were observed to have no detectable changes in the values of the MCV, the percent GR, or liver-to-body weight ratio when compared to control animals. Thus, repetitive i.p. injections of poloxamer 407 to rats at a dose of 1.0 g/kg per day for four days results in splenomegaly and a reduction in total body weight. Splenomegaly in rats administered poloxamer 407 at a dose of 1.0 g/kg per day resulted from red pulp expansion due to infiltration of macrophages which contained phagocytized lipids.

Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat

One 300 mg i.p. injection of the nonionic surfactant poloxamer 407 (Pluronic® F-127) produces a significant increase above control of both circulating cholesterol and triglyceride (TG) concentrations. The present study was conducted to determine the effect of poloxamer 407 (P-407) on the capacity to hydrolyze circulating TG by lipoprotein lipase (LPL) in an attempt to determine the mechanism of action of P-407. The concentration of TG in the rat following a single 300 mg i.p. injection of P-407 was marked, increasing from 84 ± 10 to 3175 ± 322 mg/dL at 24 hr. The maximal rate of TG accumulation (5.74 mg/dL/min) in the plasma of P-407-injected rats occurred between 2 and 4 hr post-injection. In vitro incubation of LPL with P-407 significantly inhibited enzyme activity with an inhibitory concentration at which 50% of the enzymatic activity was lost of approximately 24 μM. Concentrations of P-407 exceeding 350 μM in vitro completely inhibited LPL activity. The effects of P-407 on the enzymatic activity of LPL in post-heparin plasma obtained following a single 300 mg dose of P-407 to rats demonstrated greater than 95% suppression of LPL activity 3 hr post-injection compared with controls. Inhibition of LPL activity was greater than 90% as long as 24 hr following a single i.p. injection of P-407. However, while the heparin-releasable fraction of capillary-bound LPL was inhibited in the plasma, LPL activity significantly increased in cardiac and skeletal muscle in poloxamer-injected animals compared with sham-injected controls. Although there was no significant change in LPL activity in adipose tissue, testes, and lung resulting from P-407 treatment, LPL activity increased by 37% in myocardium, 69% in soleus, and 66% in gastronemius muscle in P-407-injected rats when compared with controls. Our studies would suggest that the predominant mechanism by which P-407 induced an increase in circulating TG was by a reduction in the rate at which TG was hydrolyzed due to inhibition of heparin-releasable LPL by the surfactant.

Thermal-induced denaturation of two model proteins: effect of poloxamer 407 on solution stability

In an attempt to enhance the physical stability of two model proteins in solution toward thermal-induced denaturation, we investigated the effect of the nonionic surfactant poloxamer 407 (Pluronic ® F-127) with a nonrecombinant (urease) and recombinant-derived (interleukin 2) protein. Our aim was to determine the time-dependent loss in biological activity when urease and recombinant interleukin-2 (rIL-2) were dissolved in pH 7 phosphate buffer (PB) with or without poloxamer 407 (P-407) and stored at elevated temperatures for 96 h. In addition, urease was selected to determine whether denaturation due to the thermal stress was reversible. Resulting percent activity remaining vs time data for each protein were fitted to a mono- (75°C) or biexponential (37 and 50°C) equation and the area-under-the-curve (AUC ¦ 0 → 96) calculated. A significantly ( p < 0.05) greater fraction of the enzymatic activity of urease was irreversibly lost when urease was dissolved in PB only and incubated at 37 and 50°C compared to urease incubated in a PB solution which contained P-407. However, for urease/PB solutions incubated at 75°C, addition of P-407 resulted in an increased rate of enzyme inactivation. Results with rIL-2 suggest that P-407 had no protective effect against thermal-induced denaturation at 50°C. Activity-time profiles described by biexponential equations may suggest an initial rapid unfolding phase followed by a slower unfolding/refolding phase for both proteins evaluated in either solvent system.

Sterie stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro

Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 μm) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8°C and 37 °C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone ( P ⩽ 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.

Polyoxyethylene–polyoxypropylene block copolymers: a novel phase transition in aqueous solutions of pluronic F87 (poloxamer 237)

An unexpected phase transition in dilute aqueous solution of the nonionic surfactant poloxamer P237 (Pluronic F87), with an excess specific heat capacity maximum at 307.7 K in the concentration range 1-10 mg/ml, has been observed using high sensitivity differential scanning calorimetry (HSDSC); the thermodynamic parameters associated with this transition are reported.

Effects of emulsified perfluorochemicals on liver cytochromes P-450 in rats

1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions or different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, have been studied separately in male and female rats. 2. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2–3 fold at 72 hr after injection of either F-DA or the novel emulsion with a less pronounced increase also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochrome concentration occurred in response to injection of FC-43 or either commercial grade or purified pluronic solution. 5. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments. 6. These results show that injection of a single low dose of emulsified PFCs into male rats can increase hepatic microsomal cytochromes P-450 concentration but the response is highly variable, depending on composition of emulsion injected.

Stabilisation of w/o/w multiple emulsions by interfacial complexation of macromolecules and nonionic surfactants

A new approach to obtain stable w/o/w multiple emulsions has been developed; the basis is the interfacial interaction between a macromolecule, e.g. albumin or polyacrylic acid in the internal aqueous, and a lipophilic poloxamer surfactant in the dispersed oil phase. Lipophilic poloxamer surfactants of high molecular weight, e.g. Poloxamer 331, were preferable in forming a stable w/o and the subsequent w/o/w emulsions. Similarly, hydrophilic poloxamer surfactants of high molecular weight could enhance the stability of the w/o/w multiple emulsions when used to emulsify the initial w/o emulsions, e.g. poloxamer 403. A water soluble, internal marker, Sulphane Blue, was encapsulated within the emulsion droplets and the release rate studies were carried out. The results revealed that both the mass transfer rate and stability of the oil membrane could be influenced by the combination of external (secondary) hydrophilic surfactants used. The secondary surfactant affected release rate primarily by control of mass transfer through the oil liquid membrane. In optimising a stable multiple emulsion formulation, both the HLB (hydrophilic-lipophilic balance) values and surface activities of the surfactants have to be considered.

Controlled Release from Crosslinked Poloxamer Hydrogels

Chemically modified derivatives of the copolymeric poloxamer surfactants have been polymerised to form crosslinked, swelling hydrogels. Mixtures of derivatives of poloxamers 188 and 181 form gels which show increased swelling with increased content of the more hydrophilic poloxamer 188. The rate of release of benzoic and p-hydroxybenzoic acids also increases with increasing content of poloxamer 188. Release rate data have been analysed in terms of the swelling controlled release model for these hydrogels.

The influence of emulsifying agents on the phagocytosis of lipid emulsions by macrophages

Abstract The phagocytosis of lipid emulsion droplets prepared from soybean oil and using various emulsifying agents has been studied in vitro using mouse peritoneal macrophages. The process of phagocytosis was first-order and dependent upon the particle size and the nature of the surface of the droplet. Systems containing anionic lipids and a non-ionic surfactant (Poloxamer) were taken up more slowly than those stabilized by simple phosphatide mixtures.

Effect of the Nonionic Surfactant Poloxamer 338 on the Fate and Deposition of Polystyrene Microspheres Following Intravenous Administration

□ The blood clearance and organ deposition of polystyrene microspheres in the rabbit following intravenous injection has been investigated using the technique of gamma scintigraphy, blood and organ level measurements, and histology. Uncoated microspheres of 1.27-μm diameter were cleared rapidly from the blood and were taken up primarily by the reticuloendothelial system in the liver. Coating of the microspheres with the nonionic surface-active agent poloxamer 338 reduced the uptake in the liver and gave a corresponding increase in the lungs.