Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polysorbates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

[Polysorb as an immobilizing matrix for the drugs used for the local therapy of otitis media].

Local treatment of inflammation by continuous introduction of the drug on the sorbent matrix is supposed to be an ideal method as it warrants prolonged supply with the drug administered in a single dose. Such treatment was given to 77 patients suffering from acute and chronic otitis media. The follow-up results show the sorbent to reduce the tissue inflammation and exudation within the initial 5-10 hours. Perforation closes much more promptly than in other treatments for acute and recurrent otitis media.

Acute Disease↗
PubMed1984

Influence of surface-active food additives on the integrity and permeability of rat intestinal mucosa.

The influence of two surface-active food additives on the integrity and permeability of rat ileal mucosa has been studied. We determined the activity of N-acetyl-beta-glucosaminidase, a lysosomal enzyme, in the rat intestinal lumen after deposition of polyoxyethylene (20) sorbitan monostearate (polysorbate 60; Tween 60) or polyoxyethylene (20) sorbitan monooleate (polysorbate 80; Tween 80) in a section of ligated, cannulated gut. We also determined the activities of N-acetyl-beta-glucosaminidase, alkaline phosphatase, 5'-nucleotidase and phospholipase A2 in mixtures of isolated mucosal cells and polysorbate 60 or polysorbate 80. The activity of N-acetyl-beta-glucosaminidase was increased in the luminal contents of the cannulated gut 15 min after deposition of either polysorbate 60 or polysorbate 80 (10 mg/ml fluid instilled into gut). It was also increased in mixtures of mucosal cells and polysorbate 60 or polysorbate 80 (0.1-10 mg/ml). In contrast, the activities of alkaline phosphatase and 5'-nucleotidase were unaffected and that of phospholipase A2 was decreased by the presence of either polysorbate. These findings indicated that polysorbate 60 and polysorbate 80 released lysosomal enzymes from the intestinal mucosal cells and that these agents might damage the intestinal mucosa and increase its permeability. We therefore determined the intestinal permeability to sodium fluorescein in the absence and presence of polysorbate 60 or 80 and found that the permeability was slightly increased in the presence of either of the compounds at concentrations of 10 mg/ml fluid instilled into gut. It is possible therefore that surface-active food additives might impair the function of the mucosal barrier and increase the permeability of the gut to potentially toxic and pathogenic molecules.

5'-Nucleotidase↗
PubMed2002

Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol.

Monomers of some amphiphiles organize into bilayers to form liposomes and niosomes. Such bilayers are unstable or leaky and hence cholesterol is a common ingredient included to stabilize them. Cholesterol stabilizes bilayers, prevents leakiness, and retards permeation of solutes enclosed in the aqueous core of these vesicles. Other than cholesterol a material with good bilayer-stabilizing properties is yet to be identified. We have substituted cholesterol with fatty alcohols in niosomes containing polyglyceryl-3-di-isostearate (PGDS) and polysorbate-80 (PS-80) to explore their membrane-stabilizing property via permeation studies. Niosomes of polyglyceryl-3-di-isostearate, fatty alcohol/cholesterol, and polysorbate were prepared by ether injection method. Aqueous solution of ketorolac tromethamine (KT) was entrapped in them. The effects of alkyl chain length of fatty alcohols (C(12), C(14), C(16), C(18), and C(16+18)), of acyl chain length of polyoxyethylene sorbitan monoester surfactants, and of the molar ratio of lipid mixture on the release rate of ketorolac from niosomes were assessed by employing modified dissolution-dialysis method. Niosomes with cholesterol or fatty alcohols have exhibited a common release pattern. Niosomes containing fatty alcohol showed a considerably slower release rate of KT than those containing cholesterol. Based on the release rate, fatty alcohols can be ranked as stearyl<myristyl<cetyl<lauryl<cetostearyl. In niosomes containing PGDS, myristyl alcohol (MA), and polysorbate, the fatty acid chain length of polyoxyethylene sorbitan ester-type surfactants has influenced the release rate and encapsulation efficiency. Based on the release rate, polysorbates can be ranked as polysorbate-20 (C(12))<polysorbate-60 (C(18))<polysorbate-80 (C(9=9))<polysorbate-40 (C(16)). In niosome preparation containing polysorbate-20 and dioctyl sodium sulfosuccinate (anionic surfactant), the release rate was slower than niosomes containing polysorbate-20. When MA concentration is kept constant at 50 mole% and the ratio of PGDS and PS-80 was altered, significant changes in entrapment efficiency and the release rate were observed. However, this ratio did not exhibit any relation with encapsulation efficiency or release rate. The release rate and entrapment exhibited an inverse correlation (r(2)=0.8774 at p<0.02 for the data of molar ratios of PGDS:MA:PS80; r(2)=0.975 at p<0.001 for the data of acyl chain length variation of polysorbates). It can be concluded that stable niosomes of polyglyceryl-3-di-isostearate could be prepared with fatty alcohols and polysorbates instead of cholesterol and that the release of solutes from these niosomes can be optimized by altering membrane constituents and their concentrations.

Cholesterol↗
PubMed2000

Effects of some non-ionic surfactants on transepithelial permeability in Caco-2 cells.

The effects of the non-ionic surfactants polysorbate 20, polysorbate 60, polysorbate 85, cholesteryl poly (24) oxyethylene ether (Solulan C24) and the lanolin-based poly (16) oxyethylene ether (Solulan 16) on the epithelial integrity of monolayers of human intestinal epithelial (Caco-2) cells has been studied using metformin as a model drug. The aim was to identify the surfactants and their optimal concentrations capable of enhancing drug transport while causing no, or only minor, cellular damage. Effects on cell permeability were assessed by measurements of the transport of metformin, a hydrophilic drug, by monitoring transepithelial electrical resistance. Cell viability was determined by the diphenyltetrazolium bromide test (the MTT test). All the surfactants studied demonstrated concentration-dependent effects on cell permeability and cell viability. The effects on transepithelial electrical resistance correlated with cell viability, i.e. increased transepithelial electrical resistance and increased cell-monolayer permeability for metformin corresponded to decreased cell viability. The results indicate that the Solulan and polysorbate surfactants were active as absorption enhancers, Solulan C24 and 16 being more effective than polysorbates 20, 60 or 85, causing an increase in metformin transport at lower concentrations than the polysorbates. Polysorbate 20 exerted its greatest effect at a concentration of 5%-increasing the flux of metformin after 3 h by a factor of around 20 over the control. Large increases in the transport of metformin, especially at surfactant levels of 0.05%, 0.1% and 0.5%, were related to the effect of Solulan C24 and Solulan 16 on the cell permeability. The Caco-2 cell monolayer experiments confirmed the ability, especially of polysorbate 20, Solulan C24 and Solulan 16, to increase the absorption of metformin. The polysorbates increased permeability as a result of solubilisation of membrane components, while Solulans did so by penetrating and solubilising the membrane. Correlation between increase in membrane permeability and the toxicity of the surfactants towards the cell membrane has been established.

Absorption↗
PubMed2002

Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier.

Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80. However, the mechanism of this transport so far was not known. In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated. Poly(butyl cyanoacrylate) nanoparticles loaded with the hexapeptide dalargin were coated with the apolipoproteins AII, B, CII, E, or J without or after precoating with polysorbate 80. In addition, loperamide-loaded nanoparticles were coated with apolipoprotein E alone or again after precoating with polysorbate 80. After intravenous injection to ICR mice the antinociceptive threshold was measured by the tail flick test. Furthermore, the antinociceptive threshold of polysorbate 80-coated dalargin-loaded nanoparticles was determined in ApoEtm1Unc and C57BL/6J mice. The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect. This effect was significantly higher after polysorbate-precoating and apolipoprotein B or E-overcoating. With the apolipoprotein E-deficient ApoEtm1Unc mice the antinociceptive effect was considerably reduced in comparison to the C57BL/6J mice. These results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB. Polysorbate 80-coated nanoparticles adsorb these apolipoproteins from the blood after injection and thus seem to mimic lipoprotein particles that could be taken up by the brain capillary endothelial cells via receptor-mediated endocytosis. Bound drugs then may be further transported into the brain by diffusion following release within the endothelial cells or, alternatively, by transcytosis.

Animals↗
PubMed2005

[Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries].

OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone). The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine associated with indomethacin, and only Nomega-nitro-L-arginine. RESULTS: Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80. CONCLUSION: The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

Amiodarone↗
PubMed2003

Reducing effect of Salvia miltiorrhiza extracts on alcohol intake: influence of vehicle.

A previous study demonstrated that an extract of Salvia miltiorrhiza, a medicinal herb highly valued in Chinese folk medicine for the treatment of different pathologies, including insomnia, was capable of reducing voluntary alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to evaluate the suitability of different emulsifying, suspending agents and solvents as vehicles through which Salvia miltiorrhiza extracts can exert their reducing effect on alcohol intake. A single dose (100 mg/kg) of a standardised extract of Salvia miltiorrhiza was dissolved in either pure Polysorbate 80, arachis oil, PEG 400, or Polyoxyl 35 castor oil, or suspended in 0.5% CMC in water, and administered acutely by gavage to sP rats. A significant and specific reduction in alcohol intake was recorded only in rats treated with the combination of Polysorbate 80 plus the Salvia miltiorrhiza extract. A further experiment demonstrated that the ability of the combination of Polysorbate 80 in water plus the Salvia miltiorrhiza extract to decrease alcohol intake was dependent upon the concentration of Polysorbate 80. The results of the present study demonstrate that Polysorbate 80 is a proper vehicle for unravelling the reducing effect of Salvia miltiorrhiza extracts on alcohol intake. The ability of Polysorbate 80 to form micelles with the active ingredient(s) of the Salvia miltiorrhiza may explain these results. They may also offer relevant information for pharmaceutical preparation of Salvia miltiorrhiza extract to be used in future clinical trials.

Alcohol Drinking↗
PubMed2001

The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients.

The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(-2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(-2), for the other three 15 ml m(-2). Prior to paclitaxel administration patients received 15 mg kg(-1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C(max)) and area under the concentration-time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(-2), paclitaxel C(max) and AUC values were 0.10 +/- 0.06 microM and 1.29 +/- 0.99 microM h(-1), respectively, whereas these values were 0.31 +/- 0.06 microM and 2.61 +/- 1.54 microM h(-1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(-2), paclitaxel excretion in faeces was 38.8 +/- 13.0% of the administered dose, whereas this value was 18.3 +/-15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel

Administration, Oral↗
PubMed2006

Delivery of hydrophobised 5-fluorouracil derivative to brain tissue through intravenous route using surface modified nanogels.

Random copolymeric micelles composed of N-isopropylacrylamide (NIPAAM) and N-vinylpyrrolidone (VP) cross-linked with N,N'-methylenebisacrylamide (MBA) have been used as nanogel carriers to encapsulate N-hexylcarbamoyl-5-fluorouracil (HCFU), a prodrug of 5-FU, and have been targeted to brain tissue across blood-brain barrier (BBB) after coating with polysorbate 80. Accumulation of nanogel particles in the brain and other tissues of "strain A" mice had been monitored by radiolabeling of nanogels with (99m)Tc. Gamma Scintigraphic technique was also performed to see the distribution of (99m)Tc labeled nanogels in the brain. The retention time in blood appeared to be slightly longer for coated nanogels than that of uncoated nanogels though the accumulation of coated nanogels in the RES was more or less same as that of uncoated nanogels. The blood however had almost double accumulation of polysorbate 80 coated nanogels in the initial 5 min compared to that shown by uncoated nanogels. We speculate that coating of nanogels with polysorbate 80 alters the surface properties of nanogels, which results in relatively higher uptake in the brain tissue. The studies revealed that a large portion of (99m)Tc labeled HCFU loaded nanogels are accumulated in the RES (lung, liver and spleen). The accumulation of the labeled nanogels in the brain, however, is much less compared to RES and it has been found that while an amount of uncoated labeled nanogels was found to be 0.18% of the injected dose, it increased to 0.52% on coating with polysorbate 80. The optimal amount of polysorbate 80 added to nanogels for the maximum delivery of particles to brain was found to be 1% w/w. These results were further supported by the gamma scintigrams of New Zealand rabbits. Thus, the present nanogel system has opened a new avenue for poorly soluble drugs to be targeted to brain by coating the particles with polysorbate 80.

Animals↗
PubMed2001

Interaction of poly(butylcyanoacrylate) nanoparticles with the blood-brain barrier in vivo and in vitro.

Poly(butylcyanoacrylate) nanoparticles were produced by emulsion polymerisation and used either uncoated or overcoated with polysorbate 80 (Tween 80). [3H]-dalargin bound to nanoparticles overcoated with polysorbate 80 or in the form of saline solution was injected into mice and the brain concentrations of radioactivity determined. Statistically significant, three-fold higher brain concentrations with the nanoparticle preparations were obtained after 45 minutes, the time of greatest pharmacological response assessed as analgesia in previous experiments. In addition the brain inulin spaces in rats and the uptake of fluoresceine isothiocyanate labelled nanoparticles in immortalised rat cerebral endothelial cells, (RBE4) were measured. The inulin spaces after i.v. injection of polysorbate 80-coated nanoparticles were significantly increased by 1% compared to controls. This is interpreted as indicating that there is no large scale opening of the tight junctions of the brain endothelium by the polysorbate 80-coated nanoparticles. In in vitro experiments endocytic uptake of fluorescent nanoparticles by RBE4 cells was only observed after polysorbate 80-overcoating, not with uncoated particles. These results further support the hypothesis that the mechanism of blood-brain barrier transport of drugs by polysorbate 80-coated nanoparticles is one of endocytosis followed by possible transcytosis. The experiments were conducted in several laboratories as part of an EEC/INTAS collaborative program. For various procedural and regulatory reasons this necessitated the use of both rats and mice as experimental animals. The brain endothelial cell line used for the in vitro studies is the rat RBE4.

Analgesics↗