INVESTIGADORES
ROMERO Eder Lilia
congresos y reuniones científicas
Título:
Nanomedicines for Chaga?s Disease & cutaneous leishmaniasis
Autor/es:
EDER ROMERO
Lugar:
Basel
Reunión:
Conferencia; The European Foundation for Clinical Nanomedicine (CLINAM) and the European Technology Platform on Nanomedicine (ETPN); 2013
Resumen:
Killing
it softly ?with lipids: on the new lethal topical vesicles against protozoa and
fungi.
Eder Lilia Romero. eder19lilia@gmail.com
Programa de Nanomedicinas. Universidad Nacional
de Quilmes, Buenos Aires, Argentina.
The
protozoa Leishmania braziliensis is the
etiological agent of muco cutaneous leishmaniasis, an endemic zoonotic disease
in South America that infects skin macrophages
to end up destroying epithelial and mucosa tissue. The parasite is capable of taking
up particulate material of size in the order of plasma proteins (< 10 nm
diameter) by the flagellar pocket (FP). This
type of endocytic uptake is limited to a small area (3 %) of the parasite body
and seems to offers a steric restriction for the uptake of higher sized particulate
material. The uptake of particulate
material by fungi such as Candida spp on the other hand, is much less explored,
but a similar steric constraint would be present. The penetration of
particulate material across the intact skin is another example of steric
restriction to be surpassed by vesicles that have to displace across
hydrophilic nanochannels of less than 10 nm diameter. Our laboratory has
developed different antifungal and antileishmania therapeutic and prophylactic
strategies, by exploiting the sterically constrained endocytic uptake of
parasites that colonize the skin surface and deeper layers combined with the
high deformability of specially designed lipid nanovesicles. In this context we
have found that in spite of their high size (~100 nm diameter) deformable nanovesicles have anti-protozoa activity per
se and that if used for non occlusive topical delivery of anti mycotic, photodynamic
agents to intracellular amastigotes or antigenic material to cells of the skin
immune system, are more effective than their non deformable counterparts of
similar size. Against Candida albicans and Candida parapsilopsis for instance,
special deformable vesicles containing Amphotericin B have 33 and 8 folds lower
MIC than Fungizone respectively, and 4 folds lower MIC than Ambisome. A low
fluence rate of 0,2 J/cm2 on ultra low doses of photodynamic deformable
vesicles at 0,01 mM ZnPC are capable of
eliminating intracellular amastigotes of Leishmania
braziliensis without killing host macrophages. In vivo, the same formulations substantially reduced the size of
lesions in Swiss mice after 5 doses plus 30 minutes of sunlight irradiation. Finally,
the topical application of a leishmania cell lysate within deformable
nanovesicles targeted against skin macrophages on the intact skin of Balb c
mice, produced antigen-specific systemic responses mediated by the induction of
the pro-inflammatory cytokines TNFa and IL6. Remarkably, these
results show that vesicles with special elasto mechanical properties can be
used not only to replace injectables but also to be efficiently taken up by the
complex endocytic machinery of eukaryotic pathogens.