Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes

Prajapati, Vijay Kumar; Awasthi, Kalpana; Gautam, Shalini; Yadav, Thakur Prasad; Rai, Madhukar; Srivastava, O. N.; Sundar, Shyam

doi:10.1093/jac/dkr002

Cited by 136 publications

(69 citation statements)

References 20 publications

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“…More recently, other groups have used the same strategy to obtain a less toxic product than free AmpB. [50][51][52][53][54] In the present work, the clinical symptoms, as well as hematological and biochemical alterations, were evaluated in the animals after the intravenous administration of saline, NQ, NQC, or NQC-AmpB nanoparticles, or free AmpB. As found in prior reports, 55,56 clinical symptoms such as ataxia, weakness, and loss of body weight were associated with the treatment using free AmpB.…”

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confidence: 99%

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Ribeiro¹,

Franca²,

Fuscaldi³

et al. 2014

IJN

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Amphotericin B (AmpB) is active against leishmaniasis, but its use is hampered due to its high toxicity observed in patients. In this study, a nanoparticles-delivery system for AmpB (NQC-AmpB), containing chitosan and chondroitin sulfate molecules, was evaluated in BALB/c mice against Leishmania amazonensis . An in vivo biodistribution study, including biochemical and toxicological evaluations, was performed to evaluate the toxicity of AmpB. Nanoparticles were radiolabeled with technetium-99m and injected in mice. The products presented a similar biodistribution in the liver, spleen, and kidneys of the animals. Free AmpB induced alterations in the body weight of the mice, which, in the biochemical analysis, indicated hepatic and renal injury, as well as morphological damage to the kidneys of the animals. In general, no significant organic alteration was observed in the animals treated with NQC-AmpB. Mice were infected with L. amazonensis and treated with the nanoparticles or free AmpB; then, parasitological and immunological analyses were performed. The NQC-AmpB group, as compared to the control groups, presented significant reductions in the lesion size and in the parasite burden in all evaluated organs. These animals presented significantly higher levels of IFN-γ and IL-12, and low levels of IL-4 and IL-10, when compared to the control groups. The NQC-AmpB system was effective in reducing the infection in the animals, and proved to be effective in diminishing the toxicity evoked by AmpB, which was observed when it was administered alone. In conclusion, NQC-AmpB could be considered a viable possibility for future studies in the treatment of leishmaniasis.

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confidence: 99%

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

Ribeiro¹,

Franca²,

Fuscaldi³

et al. 2014

IJN

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“…At least 100 cells per well (four corners and the center) were counted to determine the percentage of macrophages infected and the number of parasites per infected cell. 13,14 All experiments were performed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

In vitro Antileishmanial Drug Susceptibility of Clinical Isolates from Patients with Indian Visceral Leishmaniasis—Status of Newly Introduced Drugs

Prajapati¹,

Mehrotra²,

Gautam³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Regional variations in susceptibility of Leishmania donovani clinical isolates have been reported to antimonials but not other antileishmanial drugs. Therefore, we evaluated the susceptibility of four antileishmanial drugs in clinical use in 28 clinical isolates from endemic and non-endemic regions in the J774A.1 macrophage cell line, and we found increased tolerance of miltefosine and paromomycin in isolates from a patient from a high endemic region. Effective dose for 90% killing (ED 90 ) values were significantly higher for miltefosine (P = 0.005) and paromomycin (P = 0.02) in isolates from the high endemic region, although there were no significant differences between ED 50 values for paromomycin, miltefosine, and amphotericin B in the non-versus endemic region isolates. This report is the first of higher ED 90 values for miltefosine and paromomycin indicating susceptibility difference between regions for these newly introduced drugs by the parasite, and their use should be carefully monitored through directly observed therapy or multidrug treatment to preserve their efficacy for longer periods.

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“…However in its early ages in anti-Leishmania applications, a way of using multiwalled CNT to deliver covalently bound AmpB has been devised. 141 Unusually, this product was obtained without using any condensing agent and was thought to be covalently linked via an ether bond instead of an amide bond. The intraperitoneal administration route led to a higher percentage suppression of parasites in the spleen with CNTAmpB (89.8%) than with AmpB (68.9%).…”

Section: Bruni Et Almentioning

confidence: 99%

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Bruni¹,

Stella²,

Giraudo³

et al. 2017

IJN

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Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes

Abstract: The results of these experiments clearly demonstrate that f-CNT-AmB has significantly greater antileishmanial efficacy than AmB and had no significant cytotoxic effects.

Cited by 136 publications

References 20 publications

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

An optimized nanoparticle delivery system based on chitosan and chondroitin sulfate molecules reduces the toxicity of amphotericin B and is effective in treating tegumentary leishmaniasis

In vitro Antileishmanial Drug Susceptibility of Clinical Isolates from Patients with Indian Visceral Leishmaniasis—Status of Newly Introduced Drugs

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

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