Tissue distribution and antileishmanial activity of liposomised Amphotericin-B in Balb/c mice§

ABSTRACTThe present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency,in vitrodrug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellularLeishmania donovaniamastigotes,in vivopharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagicL. donovaniamastigotes. In thein vitrocell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs.In vivostudies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.

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Antileishmanial Activity of Amphotericin B-loaded-PLGA Nanoparticles: An Overview

Materials ◽

10.3390/ma11071167 ◽

2018 ◽

Vol 11 (7) ◽

pp. 1167 ◽

Cited By ~ 16

Author(s):

Ernesto Palma ◽

Antonella Pasqua ◽

Agnese Gagliardi ◽

Domenico Britti ◽

Massimo Fresta ◽

...

Keyword(s):

Amphotericin B ◽

Plga Nanoparticles ◽

Antileishmanial Activity

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Th-1 biased immunomodulation and synergistic antileishmanial activity of stable cationic lipid–polymer hybrid nanoparticle: Biodistribution and toxicity assessment of encapsulated amphotericin B

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2014.11.019 ◽

2015 ◽

Vol 89 ◽

pp. 62-73 ◽

Cited By ~ 25

Author(s):

Shalini Asthana ◽

Anil K. Jaiswal ◽

Pramod K. Gupta ◽

Anuradha Dube ◽

Manish K. Chourasia

Keyword(s):

Amphotericin B ◽

Cationic Lipid ◽

Toxicity Assessment ◽

Antileishmanial Activity ◽

Polymer Hybrid ◽

Hybrid Nanoparticle ◽

Th 1

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Heat Treatment of Amphotericin B Modifies Its Serum Pharmacokinetics, Tissue Distribution, and Renal Toxicity following Administration of a Single Intravenous Dose to Rabbits

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.7.2060-2063.2001 ◽

2001 ◽

Vol 45 (7) ◽

pp. 2060-2063 ◽

Cited By ~ 15

Author(s):

Evan H. Kwong ◽

Manisha Ramaswamy ◽

Emily A. Bauer ◽

Scott C. Hartsel ◽

Kishor M. Wasan

Keyword(s):

Serum Creatinine ◽

Tissue Distribution ◽

Amphotericin B ◽

Drug Administration ◽

Renal Toxicity ◽

Kidney Tissue ◽

Intravenous Dose ◽

White Female ◽

Single Intravenous Dose ◽

Time Curve

ABSTRACT The purpose of this investigation was to determine the serum pharmacokinetics, tissue distribution, and renal toxicity of amphotericin B (AmpB) following administration of a single intravenous dose (1 mg/kg of body weight) of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to New Zealand White female rabbits. FZ solutions were heated at 70°C for 20 min to produce HFZ. Blood samples were obtained before drug administration and serially thereafter. After collection of the 48-h blood sample, each rabbit was humanely sacrificed and the right kidney, spleen, lungs, liver, and heart were harvested for AmpB analysis. Serum creatinine levels were measured before and 10 h after drug administration. AmpB concentrations in the serum and tissues were analyzed using high-performance liquid chromatography. FZ administration to rabbits resulted in a greater-than-50% increase in serum creatinine concentrations compared to baseline. However, HFZ administration resulted in no difference in serum creatinine concentrations compared to baseline. The AmpB area under the concentration-time curve (AUC) after HFZ administration was significantly lower than the AmpB AUC in rabbits administered FZ. However, AmpB systemic total body clearance was significantly greater in rabbits administered HFZ than in rabbits administered FZ without any differences in volume of distribution at steady state. Kidney tissue AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. Likewise, lung and spleen AmpB concentrations, although not significantly different, were greater in rabbits administered FZ than in rabbits administered HFZ. However, liver AmpB concentrations were significantly lower in rabbits administered FZ than in rabbits administered HFZ. No significant differences in heart AmpB concentration between rabbits administered FZ and those given HFZ were found. These findings suggest that the pharmacokinetics, tissue distribution, and renal toxicity of AmpB are modified following administration of HFZ. HFZ could be an improved low-cost AmpB drug delivery system that has a potentially higher therapeutic index than FZ.

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

Natural Product Communications ◽

10.1177/1934578x19899566 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1934578X1989956 ◽

Cited By ~ 1

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.

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