INVESTIGADORES
HIGA Leticia Herminia
congresos y reuniones científicas
Título:
New Insights on Multifunctional Nano-platform Against Cutaneous Leishmaniasis
Autor/es:
LETICIA H HIGA; JORGE MONTANARI; DIANA RONCAGLIA; MARIA J MORILLA; EDER ROMERO
Lugar:
Basilea
Reunión:
Conferencia; European Summit for Clinical Nanomedicine; 2010
Institución organizadora:
European Foundation Clinical Nanomedicine
Resumen:
New Insights on Multifunctional Nano-platform Against Cutaneous
Leishmaniasis.
Higa LH, Montanari JA, Roncaglia D, Morilla MJ and
Romero EL. Programa de Nanomedicinas. Universidad Nacional de Quilmes, Buenos Aires, Argentina.
elromero@unq.edu.ar
Our laboratory has
developed the concept of multifunctional platform for the treatment of
cutaneous leishmaniasis, as UltraDeformable archaeosomes (UDa)
made of ([Total polar lipids from extremely halophilic Halorubrum tebenquichense non alkaliphilic strain, plus
carotenoids, retinal and bacterioruberin]: soy Pc: sodium
cholate 3:3:1 w/w) loaded with a hydrophobic Zn phtalocyanine as a sunlight
triggered photodynamic agent, or with a model protein ovoalbumine (OVA), for
topical immunization. We have found that UDa-ZnPc (1.25 mM ZnPc-1 mM phospholipids) elicited
100 % anti- Leishmania braziliensis promastigote activity (APA)
as well as 80 % anti amastigote activity (AA) after only 15 min sunlight
irradiation (15 J/cm2). Surprisingly empty UDa and UDa-ZnPc
also showed an extensive non-photodynamic leishmanicidal activity. Remarkably, the
phagocytosis of UDa-ZnPc by infected host cells (and not the simple diffusion of
free ZnPc) probably led to products of ZnPc metabolization that were innocuous
for the host but lethal for the parasites, even in the dark. This means that in
the absence of host cells toxicity (apoptosis/oxidative stress by GSH
consumption, release of lactate dehydrogenase, MTT) minor doses of empty UDa
or UDa-ZnPc
had got a fast and deeply in vitro destructive
effect against the extra and intracellular forms of the leishmania parasites,
which is accelerated but not triggered by sunlight irradiation. On the other hand,
two levels of OVA (0.3 mgOVA/ 0.6mg phospholipids and 0.6mg OVA/ 0.6 mg
phospholipids)/ were applied as OVA-UDa on an area of 2 cm2
in non shaved nor stripped Balb/c mice. We found that the titers of systemic IgG
resulted OVA-dosis dependent and slightly higher for 0.3 mg OVA than for 0.6 mg
OVA. This means that a threshold dose exists above which a systemic response can
not be improved. The presence of archaeolipids in the ternary matrix of UDa-OVA
should be responsible for the earlier and pronounced response that requires
lower amounts of OVA than the obtained with conventional (without archaeolipids)
ultradeformable liposomes. It is likely therefore that in vivo the leishmanicidal effect of UDa could result from a
synergistic effect fruit from its multiple leishmanicidal activity and its
superior (in the absence of penetration enhancers and organic solvent is ten-folds
as compared to conventional liposomes) capacity of penetration across the
stratum corneum.
Archaeosomes made of
Halorubrum tebenquichense total polar lipids: a new source of adjuvancy R O Gonzalez, L H
Higa, R A Cutrullis, M Bilen, I Morelli, D I Roncaglia, R S Corral, M J
Morilla, P B Petray and E L
Romero. BMC Biotechnology 2009, 9:71
Sunlight
triggered photodynamic ultradeformable liposomes against Leishmania braziliensis
are also leishmanicidal in the dark. J Montanari, C Maidana, M I
Esteva, C Salomon, M J Morilla, E L. Romero. Journal of Controlled Release, submitted March 2010.