Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity

2019 ◽  
Vol 25 (14) ◽  
pp. 1616-1622 ◽  
Author(s):  
Gabriela Muniz Félix Araújo ◽  
Gabriela Muniz Félix Araújo ◽  
Alana Rafaela Albuquerque Barros ◽  
Alana Rafaela Albuquerque Barros ◽  
João Augusto Oshiro-Junior ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Average Diameter ◽  
Isopropyl Myristate ◽  
Neglected Diseases ◽  
Clinical Form ◽  
Hydrophobic Compounds ◽  
Internal Phase ◽  
Oil In Water ◽  
Spherical Structures ◽  
Lipid Formulations

Leishmaniasis is one of the most neglected diseases in the world. Its most severe clinical form, called visceral, if left untreated, can be fatal. Conventional therapy is based on the use of pentavalent antimonials and includes amphotericin B (AmB) as a second-choice drug. The micellar formulation of AmB, although effective, is associated with acute and chronic toxicity. Commercially-available lipid formulations emerged to overcome such drawbacks, but their high cost limits their widespread use. Drug delivery systems such as nanoemulsions (NE) have proven ability to solubilize hydrophobic compounds, improve absorption and bioavailability, increase efficacy and reduce toxicity of encapsulated drugs. NE become even more attractive because they are inexpensive and easy to prepare. The aim of this work was to incorporate AmB in NE prepared by sonicating a mixture of surfactants, Kolliphor® HS15 (KHS15) and Brij® 52, and an oil, isopropyl myristate. NE exhibited neutral pH, conductivity values consistent with oil in water systems, spherical structures with negative Zeta potential value, monomodal size distribution and average diameter of drug-containing droplets ranging from 33 to 132 nm. AmB did not modify the thermal behavior of the system, likely due to its dispersion in the internal phase. Statistically similar antileishmanial activity of AmB-loaded NE to that of AmB micellar formulation suggests further exploring them in terms of toxicity and effectiveness against amastigotes, with the aim of offering an alternative to treat visceral leishmaniasis.

scholarly journals Comparative Efficacy and Distribution of Lipid Formulations of Amphotericin B in ExperimentalCandida albicansInfection of the Central Nervous System

2000 ◽  
Vol 182 (1) ◽  
pp. 274-282 ◽  
Author(s):  
Andreas H. Groll ◽  
Neelam Giri ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amphotericin B ◽  
Comparative Efficacy ◽  
The Central Nervous System ◽  
Lipid Formulations

Ordering Transitions of Semifluorinated Diblock Copolymers

2008 ◽  
Vol 8 (9) ◽  
pp. 4864-4868 ◽  
Author(s):  
Min Young Lee ◽  
Seung Ho Kim ◽  
Jong Tae Kim ◽  
Sok Won Kim ◽  
Kwon Taek Lim
Keyword(s):  
Diblock Copolymers ◽  
Average Diameter ◽  
Continuous Phase ◽  
Tem Analysis ◽  
Ordering Transitions ◽  
Cylindrical Domains ◽  
Spherical Structures ◽  
Spherical Domains ◽  
Different Shapes ◽  
Chain Lengths

A series of diblock copolymers consisting of a hydrophilic polyethylene oxide (PEO) and a hydrophobic poly(1H,1H-dihydroperfluorooctyl methacrylate) (PDHFOMA) block were synthesized with different chain lengths for application to self-assembled nanopatterning structures. The morphology of poly(DHFOMA5k-b-EO5k), poly(DHFOMA10k-b-EO10k), and poly(DHFOMA20k-b-EO20k) spin cast from micellar solution in chloroform at room temperature were spherical with average diameter of 12 nm, 17 nm and 26 nm, respectively by TEM analysis. The spherical structures were reorganized to different shapes with thermodynamically stable morphologies upon annealing above glass transition temperature (Tg). PDHFOMA block domains changed to well ordered cylindrical domains, inversed continuous phase, and large composite spherical domains for 5 k, 10 k, and 20 k block copolymer, respectively.

scholarly journals High Internal Phase Oil-in-Water Pickering Emulsions Stabilized by Chitin Nanofibrils: 3D Structuring and Solid Foam 

2020 ◽  
Vol 12 (9) ◽  
pp. 11240-11251 ◽  
Author(s):  
Ya Zhu ◽  
Siqi Huan ◽  
Long Bai ◽  
Annika Ketola ◽  
Xuetong Shi ◽  
...  
Keyword(s):  
Pickering Emulsions ◽  
Internal Phase ◽  
Oil In Water

scholarly journals Encochleated Amphotericin B: Is the Oral Availability of Amphotericin B Finally Reached?

2020 ◽  
Vol 6 (2) ◽  
pp. 66
Author(s):  
Maria Aigner ◽  
Cornelia Lass-Flörl
Keyword(s):  
Amphotericin B ◽  
The Novel ◽  
Phase Ii Clinical Trials ◽  
Wide Range ◽  
Life Threatening ◽  
Oral Availability ◽  
Reduced Toxicity ◽  
Yeasts And Molds ◽  
Lipid Formulations ◽  
Cargo Molecule

As the oldest and for many decades the only available agent for the treatment of life-threatening invasive fungal diseases, amphotericin B (AmB) is known for its broad-spectrum fungicidal activity against a wide range of yeasts and molds. However, the main drawback of the present formulations remains its toxicity, the limited use to intravenous administration, and the higher costs associated with the better tolerated lipid formulations. The novel nanoparticle-based encochleated AmB (CAmB) formulation encapsulates, protects, and delivers its cargo molecule AmB in the interior of a calcium-phospholipid anhydrous crystal. Protecting AmB from harsh environmental conditions and gastrointestinal degradation, CAmB offers oral availability in conjunction with reduced toxicity. Matinas BioPharma, Bedminster, NJ is on the way to develop CAmB named MAT2203, currently undergoing Phase II clinical trials.

Porous functional poly(unsaturated polyester-co-glycidyl methacrylate-co-divinylbenzene) polyHIPE beads through w/o/w multiple emulsions: preparation, characterization and application

e-Polymers ◽  
2014 ◽  
Vol 14 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Emine Hilal Mert ◽  
Hüseyin Yıldırım
Keyword(s):  
Glycidyl Methacrylate ◽  
Polyester Resin ◽  
Unsaturated Polyester ◽  
Aminosalicylic Acid ◽  
Adsorption Method ◽  
Multiple Emulsions ◽  
Adsorption Capacities ◽  
Internal Phase ◽  
Oil In Water ◽  
Post Functionalization

AbstractPoly(unsaturated polyester-co-glycidyl methacrylate-co-divinylbenzene) poly high internal phase emulsion (HIPE) beads were synthesized via water-in-oil-in-water (w/o/w) multiple emulsions. HIPEs were prepared by using a commercial unsaturated polyester resin (UPR) and a mixture of glycidyl methacrylate (GMA) and divinylbenzene (DVB) as the cross-linker. The external surfactant was found to be a strong influence on the morphology of the beads. The porosity and the pore morphology of the resulting polyHIPE beads were investigated by scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) molecular adsorption method, respectively. Post-functionalization of the beads was carried out with multifunctional amines such as 1,4-ethylenediamine (EDA), 1,6-hexamethylenediamine (HMDA) and 4-aminosalicylic acid (ASA). Elemental analysis was used to confirm the functionalization. Resulting functional beads were tested on the adsorption of Ag(I), Cu(II), and Cr(III) under non-competitive conditions and atomic absorption spectroscopy (AAS) was used to calculate the adsorption capacities. The maximum adsorption capacities of the functional beads were found to be decreasing in the order of Ag(I)>Cu(II)>Cr(III).

scholarly journals Pharmacokinetic-Pharmacodynamic Comparison of Amphotericin B (AMB) and Two Lipid-Associated AMB Preparations, Liposomal AMB and AMB Lipid Complex, in Murine Candidiasis Models

2006 ◽  
Vol 50 (2) ◽  
pp. 674-684 ◽  
Author(s):  
D. Andes ◽  
N. Safdar ◽  
K. Marchillo ◽  
R. Conklin
Keyword(s):  
Amphotericin B ◽  
Area Under The Curve ◽  
Dosing Regimen ◽  
Multiple Dosing ◽  
Lipid Complex ◽  
Disseminated Candidiasis ◽  
Effective Doses ◽  
The Difference ◽  
Time Kill ◽  
Lipid Formulations

ABSTRACT It is generally accepted that the lipid formulations of amphotericin B (AMB) are not as potent as conventional AMB on a milligram-per-kilogram basis. We used a neutropenic murine disseminated candidiasis model to compare the in vivo potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC) pharmacodynamically. The pharmacokinetics of the antifungals were examined in serum and in three organs commonly seeded in disseminated candidiasis (kidneys, liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen studies were used with each of the compounds. Determinations of the numbers of CFU in the kidneys were performed following the administration of three escalating single doses of the polyenes at various times over 48 h. The areas under the time-kill curves (AUTKs) for each dose level of the drugs were compared by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five Candida isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The organism burdens in the mouse kidneys were similarly used as the treatment end point. Additional multiple regimen-dosing-studies were performed with a single Candida albicans isolate, and the microbiologic outcomes in four internal organs (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h). The relationship between the dose and the drug exposure expressed by the pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed by using a maximum-effect model. ANOVA was used to compare the drug exposures necessary to achieve the 25% effective dose (ED25), ED50, ED75, and 1 log10 killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent than either ABLC or L-AMB. The time-kill curves for both lipid formulations were very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold more potent than each of the lipid formulations against five Candida isolates in the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in the other end organs. The difference in pharmacokinetics in serum accounted for much of the difference in potency between AMB and ABLC (ratio of serum ABLC area under the curve of effective doses to serum AMB area under the curve of effective doses, 1.2). The differences in the kinetics in the various end organs between AMB and L-AMB were better at explaining the disparate potencies at these infection sites (ratio of organ L-AMB area under the curve of effective doses to organ AMB area under the curve of effective doses, 1.1).

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