Passive and semi-active targeting of bone marrow and leukemia cells using anionic low cholesterol liposomes

Tardi, Paul; Wan, Chung Ping Leon; Mayer, Lawrence D.

doi:10.1080/1061186x.2016.1184669

Cited by 26 publications

(17 citation statements)

References 39 publications

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“…The blood vessels between the hematopoietic compartment and the circulation form a barrier, referred to as the marrow-blood barrier. The movement of particles through fenestrations in the endothelial wall is size dependent, ranging from 85 to 150 nm (32). In our studies, the liposomal formulation was able to deliver the buparvaquone to bone marrow macrophages, resulting in the elimination of 80% of parasites after 10 days of treatment.…”

Section: Discussionmentioning

confidence: 64%

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Costa-Silva

Galisteo

Lindoso

et al. 2017

Antimicrob Agents Chemother

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Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in Leishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the -potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 in Leishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.KEYWORDS Leishmania, drug delivery, liposomes, therapy T he worldwide prevalence and severity of leishmaniasis has led the World Health Organization to consider it a priority infectious disease (1). Due to the complexity of host-parasite interaction, as well as contradictory results from vaccination models, the control of infection is mainly dependent on chemotherapeutic intervention (2). There are now a number of therapies for various forms of leishmaniasis; the preferences for first-line and second-line treatment vary based on the type of disease and are often guided by regional practice. Pentavalent antimonials, such as Pentostam and Glucantime, have been used to treat leishmaniasis for the last 70 years (3). However, these drugs have multiple adverse effects and decreasing effectiveness due to the development of parasite resistance, limiting their application (4). In Brazil, pentavalent antimony is still effective for treating most infections, despite its high toxicity. Until now, Citation da Costa-Silva TA, Galisteo AJ, Jr, Lindoso JAL, Barbosa LRS, Tempone AG. 2017. Nanoliposomal buparvaquone immunomodulates Leishmania infantuminfected macrophages and is highly effective in a murine model. Antimicrob Agents

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Section: Discussionmentioning

confidence: 64%

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Costa-Silva

Galisteo

Lindoso

et al. 2017

Antimicrob Agents Chemother

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“…With the use of liposomes or other nanotechnology-based formulations, it will be possible to improve delivery of cytotoxic agents to the bone marrow to target leukemic stem cells. For example, liposomes have previously been shown to be preferentially taken up by bone marrow macrophages and this process facilitates the transport of drugs along with the liposomes to the bone marrow (195,196).…”

Section: Enflam - a Simpler Methods To Achieve Time Sequenced Treatmenmentioning

confidence: 99%

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Chen

Gilabert-Oriol²,

Bally

et al. 2019

Pharm Res

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Acute myeloid leukemia (AML) is the most common acute leukemia that is becoming more prevalent particularly in the older (65 years of age or older) population. For decades, “7 + 3” remission induction therapy with cytarabine and an anthracycline, followed by consolidation therapy, has been the standard of care treatment for AML. This stagnancy in AML treatment has resulted in less than ideal treatment outcomes for AML patients, especially for elderly patients and those with unfavourable profiles. Over the past two years, six new therapeutic agents have received regulatory approval, suggesting that a number of obstacles to treating AML have been addressed and the treatment landscape for AML is finally changing. This review outlines the challenges and obstacles in treating AML and highlights the advances in AML treatment made in recent years, including Vyxeos®, midostaurin, gemtuzumab ozogamicin, and venetoclax, with particular emphasis on combination treatment strategies. We also discuss the potential utility of new combination products such as one that we call “EnFlaM”, which comprises an encapsulated nanoformulation of flavopiridol and mitoxantrone. Finally, we provide a review on the immunotherapeutic landscape of AML, discussing yet another angle through which novel treatments can be designed to further improve treatment outcomes for AML patients.

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“…The process of metastasis and proliferation of malignant cells is the process of transferring cells to lymph nodes. Therefore, if the lymphatic targeting drug delivery can be conducted, the drugs will directly act on the metastasis, so that the control rate of malignant tumors can be increased [12][13][14][15] . Lymph is lipophilic, and treating the patients with malignant tumors with liposome or niosome drugs is the main idea of the current lymphatic targeting drug delivery.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic targeting drug delivery system and tumor treatment

Xiao¹

2018

2018 International Conference on Medicine, Biology, Materials and Manufacturing (ICMBMM 2018)

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Abstract.Research Objective: This study aims at observing the clinical effect of the application of the lymphatic targeting drug delivery system in the treatment of malignant tumors. Research Methods: The patients with advanced gastric cancer in our hospital are taken as the samples. According to different treatment methods, they were randomly divided into two groups, namely the observation group and the control group. The patients in the control group were treated with fluorouracil, while the patients in the observation group were treated with compound fluorouracil liposome through the application of the lymphatic targeting drug delivery system in the treatment process.Research Results: In the observation group, a total of six patients experienced adverse reactions, including five patients with nausea and vomiting and one patient with leukopenia, and the incidence rate of adverse reactions was 18.75%. The patients' five-year survival rate was 75%, and the quality of life was 86.32 ± 2.09 points. Compared with the control group, the data differences were statistically significant (p<0.05). Research Conclusions: The application of the lymphatic targeting drug compound fluorouracil liposome in the treatment of gastric cancer is of great clinical value for increasing the patients' disease control rate, improving the patients' living quality and prolonging the patients' life.

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Passive and semi-active targeting of bone marrow and leukemia cells using anionic low cholesterol liposomes

Cited by 26 publications

References 39 publications

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Lymphatic targeting drug delivery system and tumor treatment

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