Nano-Leish-IL: A novel iron oxide-based nanocomposite drug platform for effective treatment of cutaneous leishmaniasis

Kannan, Sriram; Harel, Yifat; Levy, Esthy; Dolitzky, Avishay; Sagiv, Assaf E.; Aryal, Saurav; Suleman, Laila; Lellouche, Jean‐Paul; Michaeli, Shulamit

doi:10.1016/j.jconrel.2021.05.019

Cited by 13 publications

(22 citation statements)

References 43 publications

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“…25 Therefore, the PEI/Fe ratio was 45.1/26.6 = 1.7, while the PEI polymer/Fe w/w ratio within the PEI-CAN-γ-Fe 2 O 3 NPs was 4.5 as we recently reported. 25 These w/w ratios are summarized in Table 1, with equivalent calculated molar ratios. Based on the pentamidine/Ce molar ratio for PEI DoE-Opt NPs, we estimate that per 10 Ce atoms, there are approximately 5 pentamidine molecules, but only one branched PEI bound to the surface.…”

Section: ■ Results and Discussionsupporting

confidence: 58%

“…The new batch of optimized NPs was retested in all biological assays and compared to the two nanocomposites that were reported previously by our group, 21 i.e., the original PEI-γ-Fe 2 O 3 NPs without the addition of pentamidine and the oxidized PEI OX -CAN-γ-Fe 2 O 3 NPs (Figure 9) that was shown to exhibit less nonspecific toxicity, especially in a mouse model. As can be seen (Figure 9), the MTT assay using 0.5 μg/mL of the optimized DoE NPs showed macrophage survival of 90% as with the PEI NPs 25 and 95% with the PEI OX NPs.…”

Section: ■ Results and Discussionmentioning

confidence: 80%

“…We recently reported efficient killing of several Leishmania species using the same NPs with lower toxicity (90% viability at 0.5 μg/mL). 25 Thus, the increased toxicity observed here may stem from the presence of pentamidine on the NPs. Pentamidine is used for cancer chemotherapy 27 and is released to the cytoplasm of the macrophage and may induce the additional toxicity.…”

Section: ■ Results and Discussionmentioning

confidence: 84%

“…In this context, we have recently demonstrated that PEI-CAN-γ-Fe 2 O 3 NPs can kill Trypanosoma brucei and Leishmania parasites in culture within 30 min. 25 Such functional NPs dispersed in a cream that we termed Nano-Leish-IL were also demonstrated to effectively cure cutaneous infection of L. major in mice. 25 Here, we present a functional nanosystem, which is based on a CAN-γ-Fe 2 O 3 NP core that was coordinatively grafted with both a 25 kDa branched PEI polymer and the anti-Leishmania drug, pentamidine.…”

Section: ■ Introductionmentioning

confidence: 99%

“…25 Such functional NPs dispersed in a cream that we termed Nano-Leish-IL were also demonstrated to effectively cure cutaneous infection of L. major in mice. 25 Here, we present a functional nanosystem, which is based on a CAN-γ-Fe 2 O 3 NP core that was coordinatively grafted with both a 25 kDa branched PEI polymer and the anti-Leishmania drug, pentamidine. A statistical optimization process was carried out using the MINITAB @ their efficacy in curing visceral leishmaniasis in a mouse model.…”

Section: ■ Introductionmentioning

confidence: 99%

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Novel Nanocarrier Platform for Effective Treatment of Visceral Leishmaniasis

et al. 2021

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Leishmaniasis is among the five parasitic diseases that still require the development of new drugs. Ultrasmall cerium (Ce 3/4+ ) cation-doped maghemite (γ-Fe 2 O 3 ) nanoparticles (NPs) were tested as a potential drug to treat visceral leishmaniasis, a disease affecting millions of people worldwide. The NPs were engineered for binding a polycationic branched polyethylenimine (PEI) polymer, thereby rupturing the single lysosome of these parasites and enabling entry of the anti-Leishmania drug, pentamidine. Exploiting the known lanthanide cation/complexbased coordinative chemical reactivity enabled the binding of both active agents onto the surface of the NPs. To optimize the fabrication of the cytotoxic NPs, optimization via a DoE (Design of Experiments) process was used to identify the optimal NP with toxicity against the two stages of the parasite, promastigotes, which propagate in the insect, and amastigotes, which infect the mammalian host. The screen identified a single optimized NP (DoE Opt) that was further examined in a mouse model of visceral leishmaniasis. Intravenous injection of the NPs had no adverse effects on the cellular composition or biochemical parameters of the blood, demonstrating no signs of systemic toxicity. The optimized NP was able to eradicate visceral disease caused by Leishmania donovani infection. The study demonstrates the versatile ability of the ceriumdoped NPs to bind at least two cytotoxic ligands. This approach could be used for optimizing the binding of different drugs for the treatment of other diseases, including cancer. Since resistance to treatment with nanocarriers was not reported to date, such an approach could potentially overcome drug resistance that emerges when using soluble small molecule drugs.

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Section: ■ Results and Discussionsupporting

confidence: 58%

Section: ■ Results and Discussionmentioning

confidence: 80%

Section: ■ Results and Discussionmentioning

confidence: 84%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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