Comparison of liposome based antigen delivery systems for protection against Leishmania donovani

Bhowmick, Swati; Mazumdar, Tuhina; Sinha, Roma; Ali, Nahid

doi:10.1016/j.jconrel.2009.09.018

Cited by 57 publications

(41 citation statements)

References 46 publications

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“…Studies have shown that encapsulation of antigens in liposomes, nanoparticles, or inclusion of adjuvants greatly enhances their immunogenicity and protective ability, [33][34][35] thus underscoring the need for continued studies in improving vaccine delivery. The development of a vaccine will benefit an estimated 350 million people who are at risk of developing the disease worldwide.…”

Section: Opinion: Benefits Of Continued Researchmentioning

confidence: 99%

Social and Economic Burden of Human Leishmaniasis

Okwor¹,

Uzonna²

2016

The American Society of Tropical Medicine and Hygiene

258

163

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Abstract. Leishmaniasis continues to pose a major public health problem worldwide. With new epidemics occurring in endemic areas and the spread of the disease to previously free areas because of migration, tourism, and military activities, there is a great need for the development of an effective vaccine. Leishmaniasis is a disease of the poor, occurring mostly in remote rural villages with poor housing and little or no access to modern health-care facilities. In endemic areas, diagnosis of any form of leishmaniasis puts a huge financial strain on an already meagre financial resource at both the individual and community levels. Most often families need to sell their assets (land and livestock) or take loans from informal financial outfits with heavy interest rates to pay for the diagnosis and treatment of leishmaniasis. Here, we discuss the disease with special emphasis on its socioeconomic impact on the affected individual and community. In addition, we highlight the reasons why continued research aimed at developing an effective Leishmania vaccine is necessary.

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Section: Opinion: Benefits Of Continued Researchmentioning

confidence: 99%

Social and Economic Burden of Human Leishmaniasis

Okwor¹,

Uzonna²

2016

The American Society of Tropical Medicine and Hygiene

258

163

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“…Therefore, we investigated the potential leishmanicidal activity of cationic liposomes, composed of various cationic lipids, against both SSG-sensitive and SSG-resistant L. donovani parasites, in the search for an optimal formulation of SSG to treat a nonhealing murine model of VL. but in 20 mM phosphate buffer without saline, were diluted to an appropriate volume with the same buffer, and the zeta potentials and mobilities of the particles were measured at 25°C (23).…”

mentioning

confidence: 99%

Cationic Liposomal Sodium Stibogluconate (SSG), a Potent Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani

Sinha

Roychoudhury

Palit

et al. 2015

Antimicrob Agents Chemother

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Pentavalent antimonials have been the first-line treatment for leishmaniasis for decades. However, the development of resistance to sodium stibogluconate (SSG) has limited its use, especially for treating visceral leishmaniasis (VL). The present work aims to optimize a cationic liposomal formulation of SSG for the treatment of both SSG-sensitive (AG83) and SSG-resistant (GE1F8R and CK1R) Leishmania donovani infections. Parasite killing was determined by the 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic counting of Giemsa-stained macrophages. Macrophage uptake studies were carried out by confocal microscopic imaging. Parasite-liposome interactions were visualized through transmission electron microscopy. Toxicity tests were performed using assay kits. Organ parasite burdens were determined by microscopic counting and limiting dilution assays. Cytokines were measured by enzyme-linked immunosorbent assays (ELISAs) and flow cytometry. Although all cationic liposomes studied demonstrated leishmanicidal activity, phosphatidylcholine (PC)-dimethyldioctadecylammonium bromide (DDAB) vesicles were most effective, followed by PC-stearylamine (SA) liposomes. Since entrapment of SSG in PC-DDAB liposomes demonstrated enhanced ultrastructural alterations in promastigotes, PC-DDAB-SSG vesicles were further investigated in vitro and in vivo. PC-DDAB-SSG could effectively alleviate SSG-sensitive and SSG-resistant L. donovani infections in the liver, spleen, and bone marrow of BALB/c mice at a dose of SSG (3 mg/kg body weight) not reported previously. The parasiticidal activity of these vesicles was attributed to better interactions with the parasite membranes, resulting in direct killing, and generation of a strong host-protective environment, necessitating a very low dose of SSG for effective cures. V isceral leishmaniasis (VL), caused by the protozoan parasiteLeishmania donovani, results in 0.2 to 0.4 million cases reported annually and poses a threat to about 200 million people worldwide. With the advent of the human immunodeficiency viruses, VL has surged as an opportunistic infection among AIDS patients (1). Pentavalent antimonial drugs are the first-line drugs against all forms of leishmaniasis, although their use for the treatment of VL has been discontinued in India due to the emergence of resistance. Extended treatment regimens, parenteral administration, and toxic side effects limit patient compliance with treatment. Frequent therapeutic failures due to resistance to the antimonial drug sodium stibogluconate (SSG) necessitate the use of second-line drugs such as amphotericin B (AMB), which are more toxic. Alternate therapies for VL have resulted in the development of several lipid-and liposome-based formulations of conventional drugs, with enhanced efficacies and reduced toxicities (2-7). The advantages of the use of liposomes as drug delivery vehicles for treating macrophage-resident parasites such as Leishmania involve their ease of preparation, low toxicity, and biodegradabilit...

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“…Here, we describe novel approaches to improve the protective immune response by loading Ag within NPs to further develop a Th1 response (Table 18.4). For instance, Bhowmick et al (2010) showed that cationic SA containing MLV loaded with L. donovani promastigote membrane Ag induced almost complete protection, as well as significantly high delayed-type hypersensitivity (DTH) (index of cell-mediated immunity), IgG2a antibodies, and IFN-γ. Liposomal Ag demonstrated durable cellmediated immunity, and mice challenged 10 weeks after vaccination could resist infection.…”

Section: Nanomedical Prophylactic Strategiesmentioning

confidence: 99%