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

Photodiagnosis Photodyn Ther. 2016 Mar:13:282-290. doi: 10.1016/j.pdpdt.2015.08.006. Epub 2015 Aug 22.

Abstract

Background: The shortage of drugs is a concern and has become the object of studies to discover effective alternatives for cutaneous leishmaniasis (CL) treatment. A topical formulation has been sought due to its low toxicity. Development of alternative therapies, such as multimodal ones, is important in confronting drug resistance. This study aims to compare the in vivo efficacy of topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of CL, isolated and associated with systemic therapy with miltefosine.

Methods: Five groups were adopted, each one with six isogenic adult female mice C57BL/6: (1) Negative Control-non-infected and non-treated; (2) Positive Control (PBS)-infected and non-treated; (3) Miltefosine-infected and treated with oral miltefosine 200 mg/kg/day; (4) Infected and treated with PDT with topical AlClPC (500 μL) on alternate days; (5) Oral Miltefosine 200 mg/kg/day and PDT with topical AlClPC (500 μL) on alternate days. Therapeutic schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle medium (NNN) of lymph collected from the animal paw, and animals were evaluated by paw measurement and parasitological criteria.

Results: Miltefosine associated with PDT with AlClPC promoted a significant reduction in parasite number and viability when compared to the other infected groups, also returning the paw diameter to a size similar to the negative control group after 20 days of treatment.

Conclusions: Association of miltefosine with PDT mediated by topical AlClPC represents hopes for CL treatment, an increasing dermatological disease in some countries.

Keywords: Cutaneous leishmaniasis; Liposomal chloroaluminium phthalocyanine; Miltefosine; Nanodrug; Photodynamic therapy.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / administration & dosage
  • Female
  • Indoles / administration & dosage*
  • Leishmania / drug effects*
  • Leishmania / isolation & purification
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leishmaniasis, Cutaneous / microbiology*
  • Leishmaniasis, Cutaneous / pathology
  • Liposomes / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Organometallic Compounds / administration & dosage*
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage
  • Treatment Outcome

Substances

  • Antifungal Agents
  • Indoles
  • Liposomes
  • Organometallic Compounds
  • Photosensitizing Agents
  • Phosphorylcholine
  • chloroaluminum phthalocyanine
  • miltefosine