UltraDeformable archaeosomes (UDa): a new concept on mutifunctional nano-platforms against cutaneous leishmaniasis.

LETICIA H HIGA; JORGE MONTANARI; MARIA J MORILLA; EDER L. ROMERO

Baselia

Conferencia; Clinical Nanomedicine; 2009

European Foundation Clinical Nanomedicine

The cutaneous leishmaniasis (CL) is a disabling endemic disease from the subtropical and tropical regions of Central and South America. Its treatment is long, painful and poorly effective, mainly based in parenteral administration of intralesional pentavalent antimonials. The intra-lysosomal location of leishmania amastigotes inside the poorly irrigated stratum spinosum macrophages, make the parasites highly inaccessible therapeutic targets for conventional medication. Post treatment recidivisms in mouth and nose mucosa should be consequence of the structural barriers for the access of therapeutic doses needed to impair the migration of parasites through the lymphatic system. Shorter, more efficient and less toxic treatments could be provided by nano vehicles for targeted delivery of therapeutics, that preferably exclude the use of the parenteral route.  The same applies to vaccination strategies, where the access to the antigen presenting cells at the inductive sites is mandatory in order to evoke immune protective responses. Since vesicles prepared from total polar lipids (TPL) extracted from archaeas (archaeosomes) containing polyisoprenoids glycerol ethers (archaeols) have previously shown adjuvancy upon subcutaneous and mucosal administration, here we present the concept of UDa to provide prophylactic/therapeutic and adjuvancy against CL upon topical application. The UDa are unilamellar vesicles (100 nm mean diameter) with a ternary matrix made of TPL extracted from the archaea Halorubrum tebenquichense recently found in Argentinean Patagonia (phosphatidylglycerol archaeol, phosphatidylglycerol sulphate, phosphatydylglycero archaeol phosphate, manosil-2-sulphate-(1-4)glycosil-archaeol, and a minor content of non characterized glycolipids), plus soy PC and sodium cholate at 3:3:1 w/w/w. The resulting UDa exhibited the following properties: a) deep penetration across intact human skin, as determined by cryo sectioning and fluorescence confocal microscopy observation of UDa labeled with rhodamine-PE in lipid matrix and pyranine in the inner aqueous space (1), as well as tape-stripping (2) and b) successful reconstitution post-dehydration by speed-vac, retaining their initial ultradeformability (3).