Background
Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World
Leishmania
species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by
Leishmania (Viannia) braziliensis
.
Material and Methods
Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The
in vitro
toxicity of NEs were tested
in vitro
against
L. (V.) braziliensis
and THP-1 cells. The
in vivo
toxicity was assessed in non-infected BALB/c mice.
Ex-vivo
permeation and retention studies using healthy mice skin were also conducted. Finally, the
in vivo
activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites.
Results
NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PM-loaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs.
In vivo
, the NE-PM+ClAlPc treatment did not reduce skin lesions.
Conclusion
The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols. However, the lack of efficacy in the
in vivo
model evidences that the therapeutical scheme has to be improved.
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