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. 2023 Apr 8;9(4):e15308.
doi: 10.1016/j.heliyon.2023.e15308. eCollection 2023 Apr.

Synthesis and physicochemical characterization of Zn-Al layered double hydroxides (LDHs) as a delivery system for amphotericin B: In vitro and in silico antileishmanial study

Sina Bahraminejad  1   2 , Abbas Pardakhty  2 , Iraj Sharifi  1 , Alireza Keyhani  1 , Ehsan Salarkia  1 , Mehdi Ranjbar  2   3
Affiliations

Synthesis and physicochemical characterization of Zn-Al layered double hydroxides (LDHs) as a delivery system for amphotericin B: In vitro and in silico antileishmanial study

Sina Bahraminejad et al. Heliyon. .

Abstract

Leishmaniasis as a widespread neglected vector-borne protozoan disease is a major public health concern in endemic areas due to 12 million people affected worldwide and 60,000 deaths annually. Several problems and side effects in using current chemotherapies leads to progression of new drug delivery systems against leishmaniasis. For instance, layered double hydroxides (LDHs) so-called anionic clays due to their proper characteristics, have been considered recently. In the present study, LDH nanocarriers were prepared using co-precipitation method. Then, the intercalation reactions with amphotericin B were conducted via indirect ion exchange assay. Finally, after characterization of prepared LDHs, the anti-leishmanial effects of Amp-Zn/Al-LDH nanocomposites against Leishmania major were evaluated using an in vitro and in silico model. According to results, current study demonstrated that Zn/Al-NO3 LDH nanocarriers can be used as a new promising delivery system by intercalating amphotericin B into its interlayer space for leishmaniasis treatment by eliminating the L. major parasites by remarkable immunomodulatory, antioxidant and apoptotic effects.

Keywords: Amphotericin B; Drug delivery; Layered double hydroxides; Leishmaniasis.

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Conflict of interest statement

The authors declare no conflict of interest.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
SEM images of the Zn–Al LDHs (a) amphotericin B anions intercalated into the interlayer space of Zn–Al LDHs nanocomposites after 1day (b) after 1 week (c) after 1 month (d).
Fig. 2
Fig. 2
UV–vis spectra of the Amp, Zn–Al LDHs precursor and Amp-ZnAl-LDH samples.
Fig. 3
Fig. 3
XRD pattern of the ZnAl-LDH structures (A) and ZnAl-LDH structures containing amphotericin B (B).
Fig. 4
Fig. 4
The size distribution changes of ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) during storage at 4-8 °C as an indicator of physical stability of particles.
Fig. 5
Fig. 5
Docking. A) IFN-γ consists of a central pocket and 4 cavities. B) amphotericin B (Amp B) binds to IFN-γ with the active site residues by LIGPLOT program. C) Molecular docking by Molegro Virtual Docker software. D) Predicted amino acids in pocket formation by PLIP web tool.
Fig. 6
Fig. 6
The mean inhibition rates of L. major promastigotes exposed to different concentrations of amphotericin B (Amp B), ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) in comparison to ZnAl-LDH precursor and negative control by colorimetric assay (*P < 0.001, **P < 0.01, ***P < 0.05).
Fig. 7
Fig. 7
The viability profiles of the murine macrophages exposed to various concentrations of amphotericin B (Amp B) and ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) in comparison to untreated control and LDH carrier at the concentration of 100 μg/mL after 72 h incubation. Bars demonstrate the mean ± standard deviation of viability rates (*P < 0.001).
Fig. 8
Fig. 8
Scavenging activity of various concentrations of Zn/Al-LDH nanocarrier and butylated hydroxyanisole (BHA) as a positive control on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals in comparison with untreated control. Bars represent the mean ± standard deviation of triplicate experiments.
Fig. 9
Fig. 9
Flow cytometry analysis of L. major promastigotes exposed to various concentrations of ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) and concentration of 100 μg/mL amphotericin B (Amp B) and ZnAl-LDH carrier alone in comparison with untreated control after 72 h incubation. Bars demonstrate the mean ± standard deviation of viability rates (*P < 0.001, **P < 0.01).
Fig. 10
Fig. 10
The gene expression levels of IL-12p40 (a), IFN-γ (b), and iNOS (c) associated with Th1 cell-mediated immune responses on L. major intra-macrophage amastigotes exposed to various concentrations of the ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) in comparison with untreated control. Bars demonstrate the mean ± standard deviation (*P < 0.001, **P < 0.01 and ***P < 0.05).
Fig. 11
Fig. 11
The gene expression levels of IL-10 (a) and TGF-β (b) associated with Th2 cell-mediated immune responses on L. major intra-macrophage amastigotes exposed to various concentrations of the ZnAl-LDH carriers along with amphotericin B (Amp-ZnAl-LDH) in comparison with untreated control. Bars demonstrate the mean ± standard deviation (*P < 0.001, **P < 0.01 and ***P < 0.05).
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