Evaluation of the efficacy of systemic miltefosine associated with photodynamic therapy with liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL/6 mice

Ribeiro, Jefferson Bruno Pereira; Miranda-Vilela, Ana Luisa; Graziani, Daniel; Gomes, Misléia Rodrigues de Aguiar; Amorim, Ana Angélica Santarém; Garcia, Rafaela Debastiani; Filho, José de Souza; Tedesco, Antônio Cláudio; Primo, Fernando Lucas; Moreira, Jonathan Rosa; Lima, Alexandre Vasconcelos; Sampaio, Raimunda Nonata Ribeiro

doi:10.1016/j.pdpdt.2015.08.006

Cited by 33 publications

(13 citation statements)

References 36 publications

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“…The data and our understanding of CL histopathology suggest that this effect can also be exploited as a passive targeting strategy in this context by encapsulation of antileishmanial drugs in small (<100 nm), stable (tightly packed phospholipids with cholesterol), unilamellar liposomes ( 14 ) similar to AmBisome. Indeed, several promising results have already been achieved with nanoparticles of AmB and other drugs for the treatment of CL ( 27 , 32 – 37 ).…”

Section: Discussionmentioning

confidence: 99%

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Wijnant

Bocxlaer

Yardley

et al. 2018

Antimicrob Agents Chemother

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AmBisome (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with those of the deoxycholate form of AmB (DAmB; trade name Fungizone) in murine models of Leishmania major CL. Drug levels at the target site (the localized lesion) 48 h after single intravenous (i.v.) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6, and 8). After single and multiple dosing, intralesional concentrations were 5- and 20-fold, respectively, higher than those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25, or 12.5 mg/kg (i.v.), there was a clear correlation between dose level, intralesional AmB concentration, and relative reduction in parasite load and lesion size (R2 values of >0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation.

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Section: Discussionmentioning

confidence: 99%

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Wijnant

Bocxlaer

Yardley

et al. 2018

Antimicrob Agents Chemother

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“…In 2016, the study was done on preparation of liposomal nanoparticles, the zeta potential observed was −8.2 ± 3.50 mV. It indicated that zeta potential of liposomal formulation is slightly less than MLCNPs (Ribeiro et al, 2016).…”

Section: Discussionmentioning

confidence: 98%

A novel effective therapeutic approach for treatment of Leishmania tropica through Miltefosine Loaded Chitosan Nanoparticles

Khan

Shereen

Khokhar

et al. 2020

Preprint

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Objectives The aim of the present study was to develop miltefosine loaded chitosan nanoparticles (MLCNPs) to enhance the therapeutic efficacy of conventional miltefosine drug and to compare the in vitro activities of both forms of the drug against Leishmania tropica. Methods MLCNPs were synthesized through ionic gelation with sodium tripolyphosphate (TPP). For the stabilization of nanoparticles, a controlled oxidation of MLCNPs was done with hydrogen peroxide (H2O2). The anti-leishmanial activities of MLCNP were determined by MTT cell viability colorimetric assay. The in vitro hemolysis assay was performed for assessment of toxicity in the human blood. Results The MLCNPS displayed spherical shape with irregular surface morphology, had a mean size of 200nm and a zeta potential of +10.9 ± 4 mV. A high encapsulation efficacy and drug loading capacity of miltefosine loaded chitosan nanoparticles was also observed. The anti-leishmanial activities of MLCNP were determined by MTT cell viability colorimetric assay. The IC50 value of MLCNPs against promastigote and amastigote were recorded as 0.85µg/ml and 0.92µg/ml respectively. MLCNPs proved to be more effective as compared to conventional miltefosine. In terms of toxicity the MLCNPs caused only 2.25% hemolysis. Conclusions The engineered MLCNPs could be potential alternative for the treatment of cutaneous leishmaniasis.

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“…Another interesting approach is the combination of the PDT and the use of current antileishmanial drugs. In this context, Ribeiro et al [103] developed an AlClPC and combined it with the drug miltefosine to evaluate the synergistic effect, which showed high leishmanicidal activity.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…For instance, the phthalocyanine chlorosaluminum liposome compound (AlClPC) was developed through nanotechnology techniques for controlled drug release, improving the drug bioavailability and diminishing the drug toxicity; thus this PS was evaluated in association with miltefosine in an in vivo CL model. Although this promising therapeutic approach is able to decrease the parasite load in the site of infection and could be done without hospitalization, the authors did not investigate its toxicity to date [103].…”

Section: Cutaneous Leishmaniasismentioning

confidence: 99%

“…Indeed, Vianna and cols [104] demonstrated that photo-inactivated parasites used as vaccine may modulate the immune response of susceptible BALB/c mice, and prophylactics protecting them against challenging infections [104]. Table 5 shows the details of the parameters and results used in the studies related to PDT and cutaneous leishmaniasis [102,103,104,105,106,107,108,109].…”

Section: Cutaneous Leishmaniasismentioning

confidence: 99%

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Chlorin, Phthalocyanine, and Porphyrin Types Derivatives in Phototreatment of Cutaneous Manifestations: A Review

Annunzio

Costa

Mezzina

et al. 2019

IJMS

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Recent scientific research has shown the use of chlorin, phthalocyanines, and porphyrins derivatives as photosensitizers in photodynamic therapy in the treatment of various pathologies, including some of the major skin diseases. Thus, the main goal of this critical review is to catalog the papers that used these photosensitizers in the treatment of acne vulgaris, psoriasis, papillomavirus infections, cutaneous leishmaniasis, and skin rejuvenation, and to explore the photodynamic therapy mechanisms against these conditions alongside their clinical benefits.

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Evaluation of the efficacy of systemic miltefosine associated with photodynamic therapy with liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL/6 mice

Cited by 33 publications

References 36 publications

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

A novel effective therapeutic approach for treatment of Leishmania tropica through Miltefosine Loaded Chitosan Nanoparticles

Chlorin, Phthalocyanine, and Porphyrin Types Derivatives in Phototreatment of Cutaneous Manifestations: A Review

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