Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

Banerjee, Saumyabrata; De, Manjarika; Ali, Nahid

doi:10.1128/aac.00524-10

Cited by 43 publications

(37 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PM formulations have some disadvantages, including a short half-life in plasma and rapid renal excretion (being a hydrophilic molecule with high molecular weight). All these factors decrease the concentration of PM at the sites of action, e.g., the reduction of PM oral absorption, thus making the oral administration of PM inefficient (8,9,12,14). According to the data obtained from clinical trials, the effect of the topical form of PM for the treatment of cutaneous leishmaniasis has been promising, but due to the powerful barrier nature of the skin, it is not effective (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, colloidal carriers, such as liposomes, emulsions, and polymeric nanoparticles, have been very promising in improving the bioavailability of the active pharmaceutical ingredients (9,42,43). In one recent study, PM-loaded liposomes were developed and investigated as a drug delivery system (8,9,12,14). The effect of PM formulated with stearylamine-bearing liposome on visceral leishmaniasis was investigated by Banerjee et al (8).…”

Section: Discussionmentioning

confidence: 99%

“…In one recent study, PM-loaded liposomes were developed and investigated as a drug delivery system (8,9,12,14). The effect of PM formulated with stearylamine-bearing liposome on visceral leishmaniasis was investigated by Banerjee et al (8). Jaafari et al (2009) evaluated the effect of PM sulfate formulated with liposomes in the treatment of L. major-infected mice (9).…”

Section: Discussionmentioning

confidence: 99%

“…Due to the antimonial resistance issue, amphotericin B (AMB) has been introduced as a first-line treatment. Its toxicity along with its cost are the most highlighted limitations of its utilization (7,8). One of the most promising drugs for anti-leishmanial chemotherapy is paromomycin sulfate (PM).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

et al. 2015

View full text Add to dashboard Cite

Abstract. Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising antileishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P<0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.KEY WORDS: cutaneous leishmaniasis; drug delivery system; paromomycin sulfate; solid lipid nanoparticle.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To check for any toxic effects of compound 5f on the liver, the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and bilirubin (both conjugated and unconjugated) were measured using kits from Span Diagnostics Limited (Surat, India) (38). To check for any toxic effects of compound 5f on the kidneys, the serum urea and creatinine levels were analyzed using kits from Span Diagnostics (38). To monitor the effect of compound 5f on other blood parameters, the hemoglobin content was measured, along with a total count of blood cells and a differential count of white blood cells from mice blood exposed to compound 5f (50 mg kg Ϫ1 day Ϫ1 ) for 4 successive days.…”

mentioning

confidence: 99%

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones

Sarkar

Siddiqui

Saha

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bWe synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (K D [equilibrium dissociation constant] ‫؍‬ 1.17 ؎ 0.8 M), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structureactivity relationship studies indicated that a nitrogen-and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [ 3 H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria.

show abstract