Promising nanotherapy in treating leishmaniasis

Publication date: 25 August 2018Source: International Journal of Pharmaceutics, Volume 547, Issues 1–2Author(s): Aline de Souza, Débora Soares Souza Marins, Samir Leite Mathias, Lis Marie Monteiro, Megumi Nishitani Yukuyama, Cauê Benito Scarim, Raimar Löbenberg, Nádia Araci Bou-ChacraAbstractLeishmaniases are infectious diseases caused by an intracellular protozoan in humans by 20 different species of Leishmania among more than 53 species. There are at least twelve million cases of infections worldwide and three hundred and fifty million people are at risk in at least 98 developing countries in Africa, South-East Asia, and the Americas. Only Brazil presented high burden for both visceral leishmaniasis (VL) and cutaneous (CL). Chemotherapy is the main means of dealing with this infection. Nevertheless, only a few effective drugs are available, and each has a particular disadvantage; toxicity and long-term regimens compromise most chemotherapeutic options, which decreases patient compliance and adherence to the treatment and consequently the emergence of drug-resistant strains. Nano drug delivery systems (NanoDDS) can direct antileishmanial drug substances for intracellular localization in macrophage-rich organs such as bone marrow, liver, and spleen. This strategy can improve the therapeutic efficacy and reduce the toxic effects of several antileishmanial drug substances. This review is an effort to comprehensively compile recent findings, with t...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Conclusions/SignificanceTaken together, these results suggest 2HF as a potential candidate for leishmaniasis chemotherapy for cutaneous leishmaniasis caused by both wild-type and antimony-resistantLeishmania species by oral administration. Furthermore, studies should be conducted to determine the ideal dose and therapeutic regimen.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
In this study, the in vitro leishmanicidal activities of several organo- selenium and sulfur compounds were tested against Leishmania major and Leishmania amazonensis parasites, using promastigotes and intracellular amastigote forms. The cytotoxicity of these agents was measured in murine peritoneal macrophages and their selectivity indexes were calculated. One of the tested compounds, an isoselenocyanate derivative NISC-6, showed selectivity indexes two- and ten-fold higher than those of the reference drug Amphotericin B when evaluated in L. amazonensis and L. major, respectively. The American strain (L. amazonensis) was ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
CONCLUSION: Our results demonstrate that both the SEDDS formulations of curcumin have the potential to provide a promising tool for curcumin for its use through topical routes in the treatment of cutaneous and mucocuatenous leishmaniasis. PMID: 30360717 [PubMed - as supplied by publisher]
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research
Abstract Leishmaniasis is a dreaded disease caused by protozoan parasites belonging to the genus Leishmania which results in significant morbidity and mortality worldwide. There are no vaccines available currently for the treatment of Leishmaniasis and chemotherapy still remains the mainstay for anti-leishmanial therapeutics. However, toxicity, reduced bioavailability, high cost and chemoresistance are the principal problems which limit the use of the available drugs. In this context, anti-leishmanial nanotherapeutics may show the way for effective treatment of this dreaded disease. In this review, we discuss the ...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Metab Source Type: research
Abstract Leishmaniasis affects over 150 million people all over the world, especially in subtropical regions. Currently used antileishmanial synthesized drugs are associated with some drawbacks such as resistance and cytotoxicity, which hamper the chances of treatment. Furthermore, effective leishmanial vaccines are not well developed. Promising chemotherapy, either from natural or synthetic compounds, was or still is the most promising treatment. This review focuses on recent findings in drugs used for the treatment of leishmaniasis including; chemical and natural antileishmanial moieties, different potential tar...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
López-Gonzálvez Á, Rivas L Abstract Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insig...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Abstract Oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the year 2002 for the treatment of visceral leishmaniasis (VL). However, recent reports on its declining efficacy and increasing relapse rates pose a serious concern. An understanding of the factors contributing to MIL tolerance in Leishmania parasites is critical. In the present study, we assessed the role of lipase precursor like protein (Lip) in conferring tolerance towards miltefosine by episomally overexpressing Lip into L. donovani (LdLip++). We observed significant increase (∼3 fold) in MIL IC50 both at promastigote (3.90 ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
We present a  case ofVisceral Leishmaniasis (VL) in a  patient with gastric cancer treated with chemoradiotherapy. A 69-year-old man with gastric carcinoma had been treated with total gastrectomy, lymphadenectomy and postoperative radiotherapy with chemotherapy. Then 3 years after treatment, due to pancytopenia with progressive trombocytopenia and s plenomegaly, bone marrow examination was performed and Leishmania spp. amastigotes were diagnosed. When antibiotherapy was completed, splenomegaly was eliminated and the laboratory results became normal. VL should be kept in mind in the differential diagnosi...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Kinetoplastid and apicomplexan parasites comprise a group of protozoans responsible for human diseases, with a serious impact in human health and the socioeconomic growth of developing countries. Chemotherapy is the main option to control these pathogenic organisms and nucleotide metabolism is considered a promising area for the provision of antimicrobial therapeutic targets. Impairment of thymidylate (dTMP) biosynthesis severely diminishes the viability of parasitic protozoa and the absence of enzymatic activities specifically involved in the formation of dTMP (e.g. dUTPase, thymidylate synthase, dihydro...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
by Jair L. Siqueira-Neto, Anjan Debnath, Laura-Isobel McCall, Jean A. Bernatchez, Momar Ndao, Sharon L. Reed, Philip J. Rosenthal Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact:Entamoeba hist...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
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