Lipid emulsions as a novel system to reduce the hemolytic activity of lytic agents: mechanism of the protective effect

Jumaa, Muhannad; Müller, Bernd W.

doi:10.1016/s0928-0987(99)00071-8

Cited by 72 publications

(27 citation statements)

References 25 publications

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“…Consequently, AZM has only a limited direct contact with the tested blood cells and is not easily partitioned from oil phase to water phase of the macroemulsion, resulting in the loss of its hemolytic activity. Such a mechanism has been suggested for other lytic agents (29). Similar observations were also seen previously for AZM when incorporating it into the non-phospholipid-based cationic oil-inwater nanosized emulsion (13) or/and into PEG-based microparticles (28).…”

Section: Discussionsupporting

confidence: 82%

In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management

Shunmugaperumal

Kaur

2015

AAPS PharmSciTech

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Abstract. The objectives of the current investigation are (1) to prepare and characterize (particle size, surface charge (potential zeta), surface morphology by transmission electron microscopy, drug content, and drug release) the azithromycin (AZM, 100 mg)-loaded oil-in-water (o/w) macroemulsion, (2) to assess the toxicity of macroemulsion with or without AZM using RBC lysis test in comparison with AZM in phosphate buffer solution of pH 7.4, (3) to compare the in vitro antimicrobial activity (in Escherichia coli using zone inhibition assay) of AZM-loaded macroemulsion with its aqueous solution, and (4) to assess the in vitro anti-inflammatory effect (using egg albumin denaturation bioassay) of the AZM-loaded macroemulsion in comparison with diclofenac sodium in phosphate buffer solution of pH 7.4. The AZM-loaded macroemulsion possessed the dispersed oil droplets with a mean diameter value of 52.40± 1.55 μm. A reversal in the zeta potential value from negative (−2.16±0.75 mV) to positive (+6.52± 0.96 mV) was noticed when AZM was added into the macroemulsion. At a 1:5 dilution ratio, 2.06± 0.03 mg of drug was released from macroemulsion followed by 1.01±0.01 and 0.25±0.08 mg, respectively, for 1:10 and 1:40 dilution ratios. Antimicrobial activity maintenance and significant reduction of RBC lysis property were noticed for AZM after loaded in the macroemulsion. However, an increment in the absorbance values for emulsion-treated samples in comparison to the control samples was noticed in the anti-inflammatory test. This speculates the potential of the AZM-loaded emulsion to manage inflammatory conditions produced at Acne vulgaris.

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Section: Discussionsupporting

confidence: 82%

In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management

Shunmugaperumal

Kaur

2015

AAPS PharmSciTech

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“…Consequently, cardol has limited direct contact with the tested blood cells, and is not easily partitioned into them, resulting in the loss of its hemolytic activity. Such a mechanism has been suggested for other lytic agents [1]. The studied formulations, which contained only a 2.4% w/w oil phase, are sufficient cardol carriers.…”

Section: Resultsmentioning

confidence: 80%

“…They minimize the side effects of the incorporated drugs and can easily be produced on a large scale. The drug-induced hemolysis of erythrocytes can also be avoided via incorporation into a lipid emulsion [1]. In our previous study, we demonstrated that the oil from the seeds of the tropical deciduous tree Adenanthera pavonina L. (Leguminosae) could be used as a valuable matrix for forming stable lipid emulsions [2].…”

Section: Introductionmentioning

confidence: 99%

Emulsions of oil from Adenanthera pavonina L. seeds and their protective effect

Jaromin

Żarnowski

Kozubek

2006

Cellular and Molecular Biology Letters

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Abstract:In our previous study, we developed very stable formulations of submicron oil-in-water emulsions from Adenanthera pavonina L. (family Leguminosae, subfamily Mimosoideae) seed oil, stabilised with soybean lecithin (SPC). Continuing our research, we introduced an additional co-emulsifier, Tween 80, to those formulations in order to decrease the size of the emulsion particles and improve their stability. Formulations with a mean particle size ranging from 43.6 to 306.5 nm and a negative surface charge from -45.3 to -28.5 mV were obtained. Our stability experiments also revealed that most of the tested formulations had a very good degree of stability over a 3-month storage period, both at 4ºC and at room temperature. Since many intravenous injectable drugs exhibit lytic activity against erythrocytes, we examined this activity for the emulsion form of cardol, a natural compound with already proven hemolytic properties. The incorporation of this agent into the emulsion caused an evident decrease in hemolytic activity (97-99%). This highly protective effect, observed against sheep erythrocytes, was independent of both the composition and the particle size of the emulsions used. Our studies suggest that nonionic surfactant/phospholipid-based emulsions containing this edible oil of A. pavonina L. may be useful as an alternative formulation matrix for pharmaceutical, nutritional or cosmetic applications of otherwise membrane-acting components.

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“…The use of phosphatidylcholine mixed with polyethylene oxide-based surfactants, such as Labrasol, dramatically reduces the toxicity of the latter, as already observed and discussed. 55 Though we used low percentages of nonionic surfactant, F5 meets the criteria to be classified as SEDDS type IIIA, with good capability to solubilize RAV, high stability upon dilution, and safe characteristics in vivo. Although the promising physicochemical properties of lipid-based drug delivery systems, particularly of SEDDS, have generated enthusiasm in the pharmaceutical industry, there is already some reticence in developing and commercializing such formulations due to the absence of information regarding toxic effects of the vehicle, particularly in vivo.…”

Section: T Cruzi-infected Micementioning

confidence: 99%

Ravuconazole self-emulsifying delivery system: in vitro activity against <em>Trypanosoma cruzi</em> amastigotes and in vivo toxicity

Spósito

Mazzeti

Faria

et al. 2017

IJN

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Self-emulsifying drug delivery systems (SEDDSs) are lipid-based anhydrous formulations composed of an isotropic mixture of oil, surfactant, and cosurfactants usually presented in gelatin capsules. Ravuconazole (Biopharmaceutics Classification System [BCS] Class II) is a poorly water-soluble drug, and a SEDDS type IIIA was designed to deliver it in a predissolved state, improving dissolution in gastrointestinal fluids. After emulsification, the droplets had mean hydrodynamic diameters <250 nm, zeta potential values in the range of −45 mV to −57 mV, and showed no signs of ravuconazole precipitation. Asymmetric flow field-flow fractionation with dynamic and multiangle laser light scattering was used to characterize these formulations in terms of size distribution and homogeneity. The fractograms obtained at 37°C showed a polydisperse profile for all blank and ravuconazole–SEDDS formulations but no large aggregates. SEDDS increased ravuconazole in vitro dissolution extent and rate (20%) compared to free drug (3%) in 6 h. The in vivo toxicity of blank SEDDS comprising Labrasol ® surfactant in different concentrations and preliminary safety tests in repeated-dose oral administration (20 days) showed a dose-dependent Labrasol toxicity in healthy mice. Ravuconazole–SEDDS at low surfactant content (10%, v/v) in Trypanosoma cruzi -infected mice was safe during the 20-day treatment. The anti- T. cruzi activity of free ravuconazole, ravuconazole–SEDDS and each excipient were evaluated in vitro at equivalent ravuconazole concentrations needed to inhibit 50% or 90% (IC 50 and IC 90 ), respectively of the intracellular amastigote form of the parasite in a cardiomyocyte cell line. The results showed a clear improvement of the ravuconazole anti- T. cruzi activity when associated with SEDDS. Based on our results, the repurposing of ravuconazole in SEDDS dosage form is a strategy that deserves further in vivo investigation in preclinical studies for the treatment of human T. cruzi infections.

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Lipid emulsions as a novel system to reduce the hemolytic activity of lytic agents: mechanism of the protective effect

Cited by 72 publications

References 25 publications

In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management

In Vitro Anti-inflammatory and Antimicrobial Activities of Azithromycin After Loaded in Chitosan- and Tween 20-Based Oil-in-Water Macroemulsion for Acne Management

Emulsions of oil from Adenanthera pavonina L. seeds and their protective effect

Ravuconazole self-emulsifying delivery system: in vitro activity against <em>Trypanosoma cruzi</em> amastigotes and in vivo toxicity

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