Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania major

Nanomedicine ◽  
2018 ◽  
Vol 13 (24) ◽  
pp. 3129-3147 ◽  
Author(s):  
Tahereh Zadeh Mehrizi ◽  
Mehdi Shafiee Ardestani ◽  
Mostafa Haji Molla Hoseini ◽  
Ali Khamesipour ◽  
Nariman Mosaffa ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Considerable Improvement

scholarly journals Leishmanicidal Activity of Isoselenocyanate Derivatives

2018 ◽  
Vol 63 (2) ◽  
pp. e00904-18 ◽  
Author(s):  
Celia Fernández-Rubio ◽  
Esther Larrea ◽  
José Peña Guerrero ◽  
Eduardo Sesma Herrero ◽  
Iñigo Gamboa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amphotericin B ◽  
Cell Cycle Progression ◽  
Leishmania Major ◽  
Antitumor Agents ◽  
Peritoneal Macrophages ◽  
Reference Drug ◽  
Content Type ◽  
Leishmanicidal Activity

ABSTRACTConventional chemotherapy against leishmaniasis includes agents exhibiting considerable toxicity. In addition, reports of drug resistance are not uncommon. Thus, safe and effective therapies are urgently needed. Isoselenocyanate compounds have recently been identified with potential antitumor activity. It is well known that some antitumor agents demonstrate effects againstLeishmania. In this study, thein vitroleishmanicidal activities of several organo-selenium and organo-sulfur compounds were tested againstLeishmania majorandLeishmania amazonensisparasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, the isoselenocyanate derivative NISC-6, showed selectivity indexes 2- and 10-fold higher than those of the reference drug amphotericin B when evaluated inL. amazonensisandL. major, respectively. The American strain (L. amazonensis) was less sensitive to NISC-6 thanL. major, showing a trend similar to that observed previously for amphotericin B. In addition, we also observed that NISC-6 significantly reduced the number of amastigotes per infected macrophage. On the other hand, we showed that NISC-6 decreases expression levels ofLeishmaniagenes involved in the cell cycle, such astopoisomerase-2(TOP-2),PCNA, andMCM4, therefore contributing to its leishmanicidal activity. The effect of this compound on cell cycle progression was confirmed by flow cytometry. We observed a significant increase of cells in the G1phase and a dramatic reduction of cells in the S phase compared to untreated cells. Altogether, our data suggest that the isoselenocyanate NISC-6 may be a promising candidate for new drug development against leishmaniasis.

scholarly journals Antileishmanial Potential of Propolis Essential Oil and Its Synergistic Combination With Amphotericin B

2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X1989956 ◽  
Author(s):  
Ayari Jihene ◽  
Essid Rym ◽  
Karoui Jabri Ines ◽  
Hammami Majdi ◽  
Tabbene Olfa ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Essential Oil ◽  
Amphotericin B ◽  
Leishmania Major ◽  
Antileishmanial Activity ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Spectrometry Analysis ◽  
Low Cytotoxicity ◽  
Promising Source

The antileishmanial activity of Tunisian propolis essential oil (EO) and its combination with amphotericin B was investigated against 2 local clinical strains of Leishmania: Leishmania major and Leishmania infantum. The cytotoxic potential of this EO was evaluated against macrophage Raw264.7. Combination of propolis EO and amphotericin B was investigated using the checkerboard method. The propolis sample was collected from the region of Beni Khalled, a Tunisian city located west of Cape Bon (Nabeul). Its location is particular since it is near to sea with a steppe climate and the predominance of citrus trees. The EO was obtained by Clevenger-type apparatus. Its chemical composition was identified using gas chromatography with flame ionization detector and gas chromatography-mass spectrometry analysis. Our results demonstrate that Tunisian propolis EO exhibit good antileishmanial activity against L. major and L. infantum promastigotes (IC50 = 5.29 ± 0.31 and 3.67 ± 0.52 µg/mL, respectively) and amastigotes (IC50 = 7.38 ± 0.45 and 4.96 ± 0.24 µg/mL, respectively). Moreover, it reduced significantly the parasite proliferation on a dose-dependent response (95%) with low cytotoxicity (selectivity index = 16.18 and 23.33, respectively). Its combination with amphotericin B showed a synergistic potential (fractional inhibitory concentration = 0.37). Interestingly, the data suggest that propolis EO was involved in macrophage activation by hyperproduction of NO. A total of 51 compounds were identified in the propolis EO. The major compound identified was α-pinene (36.7% ± 2.36%) followed by α-cedrol (6.7% ± 0.10%), totarol (6.6% ± 0.09%), and dehydroabietane (5.2% ± 0.10%). Our findings suggest that Tunisian propolis might constitute a promising source for antileishmanial molecules.

scholarly journals An amphotericin B-based drug for treating experimental Leishmania major infection

2010 ◽  
Vol 104 (11) ◽  
pp. 749-750 ◽  
Author(s):  
Karina D. Corware ◽  
Matthew Rogers ◽  
Ian Teo ◽  
Ingrid Müller ◽  
Sunil Shaunak
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Major Infection

scholarly journals Efficacious Treatment of Experimental Leishmaniasis with Amphotericin B-Arabinogalactan Water-Soluble Derivatives

1999 ◽  
Vol 43 (9) ◽  
pp. 2209-2214 ◽  
Author(s):  
Jacob Golenser ◽  
Shoshana Frankenburg ◽  
Tirtsa Ehrenfreund ◽  
Abraham J. Domb
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Water Soluble ◽  
In Vivo Experiments ◽  
Drug Concentrations ◽  
Efficacious Treatment ◽  
Lipid Formulations ◽  
Established Infection

ABSTRACT In this study, we tested the efficacy of amphotericin B (AmB)-arabinogalactan (AmB-AG) conjugates for the treatment of experimental leishmaniasis. Chemical conjugation of AmB to a water-soluble, biodegradable, and biocompatible polymer could present many advantages over presently available AmB formulations. Two conjugates were tested, a reduced (rAmB-AG) form and an unreduced (uAmB-AG) form. In vitro, the drug concentrations which lower the values of parasites (for promastigotes) or infected macrophages (for amastigotes) to 50% of the untreated values (ED50s) of uAmB-AG and rAmB-AG were 0.19 and 0.34 μg/ml, respectively, forLeishmania major promastigotes and 0.17 and 0.31 μg/ml, respectively, for amastigotes. The effect on Leishmania infantum-infected macrophages was more marked, with ED50s of 0.035 μg/ml for rAmB-AG and 0.027 μg/ml for uAmB-AG. In in vivo experiments, BALB/c mice injected with L. major were treated from day 2 onwards on alternate days for 2 weeks. Both conjugates, as well as liposomal AmB (all at 6 mg/kg of body weight) and Fungizone (1 mg/kg), significantly delayed the appearance of lesions compared to that in untreated mice. In addition, both conjugates, but not liposomal AmB, were significantly more effective than Fungizone. Subcutaneous injection of the conjugates (6 mg/kg) was significantly more effective than liposomal AmB in delaying the appearance of lesions. Higher AmB concentrations of up to 12 mg/kg could be administered by this route. When an established infection was treated, uAmB-AG was somewhat more effective than liposomal AmB. In summary, water-soluble polymeric AmB derivatives were found effective and safe for the treatment of leishmanial infections. The conjugates, which are stable and can be produced relatively cheaply (compared to lipid formulations), can be used in the future for the treatment of leishmaniasis infections.

scholarly journals Biodistribution and In Vivo Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl-sn-Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Maryam Iman ◽  
Zhaohua Huang ◽  
Seyedeh Hoda Alavizadeh ◽  
Francis C. Szoka ◽  
Mahmoud R. Jaafari
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Parasite Load ◽  
Tissue Concentrations ◽  
Content Type ◽  
Colloidal Properties ◽  
Covalently Linked ◽  
Antileishmanial Activities

ABSTRACT 1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (P < 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The in vivo activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.

Reduction toxicity of Amphotericin B through loading into a novel nanoformulation of anionic linear globular dendrimer for improve treatment of leishmania major

2018 ◽  
Vol 29 (8) ◽  
Author(s):  
Tahereh Zadeh Mehrizi ◽  
Mehdi Shafiee Ardestani ◽  
Ali Khamesipour ◽  
Mostafa Haji Molla Hoseini ◽  
Nariman Mosaffa ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Major ◽  
Improve Treatment

Leishmania major infection in a patient with visceral leishmaniasis: treatment with Amphotericin B

2007 ◽  
Vol 101 (5) ◽  
pp. 1431-1434 ◽  
Author(s):  
Mehdi Karamian ◽  
Mohammad Hossein Motazedian ◽  
Davood Mehrabani ◽  
Khodakaram Gholami
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Major ◽  
Major Infection

scholarly journals Lathosterol oxidase (sterol C5-desaturase) deletion confers resistance to amphotericin B and sensitivity to acidic stress in Leishmania major

2020 ◽  
Author(s):  
Yu Ning ◽  
Cheryl Frankfater ◽  
Fong-Fu Hsu ◽  
Rodrigo P. Soares ◽  
Camila A. Cardoso ◽  
...  
Keyword(s):  
Double Bond ◽  
Amphotericin B ◽  
Leishmania Major ◽  
Pathogenic Fungi ◽  
New Drugs ◽  
Sterol Synthesis ◽  
Null Mutant ◽  
Biologically Relevant ◽  
Membrane Components ◽  
Triton X

ABSTRACTLathosterol oxidase (LSO) catalyzes the formation of C5-C6 double bond in the synthesis of various types of sterols in mammals, fungi, plants and protozoa. In Leishmania parasites, mutations in LSO or other sterol biosynthetic genes are associated with amphotericin B resistance. To investigate the biological roles of sterol C5-C6 desaturation, we generated a LSO-null mutant line (lso–) in Leishmania major, the causative agent for cutaneous leishmaniasis. Lso– parasites lacked the ergostane-based sterols commonly found in wild type L. major and instead accumulated equivalent sterol species without the C5-C6 double bond. These mutant parasites were replicative in culture and displayed heightened resistance to amphotericin B. However, they survived poorly after reaching the maximal density and were highly vulnerable to the membrane-disrupting detergent Triton X-100. In addition, lso– mutants showed defects in regulating intracellular pH and were hypersensitive to acidic conditions. They also had potential alteration in the carbohydrate composition of lipophosphoglycan, a membrane-bound virulence factor in Leishmania. All these defects in lso– were corrected upon the restoration of LSO expression. Together, these findings suggest that the C5-C6 double bond is vital for the structure of sterol core, and while the loss of LSO can lead to amphotericin B resistance, it also makes Leishmania parasites vulnerable to biologically relevant stress.IMPORTANCESterols are essential membrane components in eukaryotes and sterol synthesis inhibitors can have potent effects against pathogenic fungi and trypanosomatids. Understanding the roles of sterols will facilitate the development of new drugs and counter drug resistance. Lathosterol oxidase (aka sterol C5-desaturase) is required for the formation of C5-C6 double bond in the sterol core structure in mammals, fungi, protozoans, plants and algae. Functions of this C5-C6 double bond are not well understood. In this study, we generated and characterized a lathosterol oxidase-null mutant in Leishmania major. Our data suggest that the C5-C6 double bond is vital for the structure and membrane-stabilizing functions of leishmanial sterols. In addition, our results imply that while mutations in lathosterol oxidase can confer resistance to amphotericin B, an important antifungal and antiprotozoal agent, the alteration in sterol structure leads to significant defects in stress response that could be exploited for drug development.

Sign in / Sign up

Export Citation Format

Share Document