title: Ultradeformable Archaeosomes for Needle Free Nanovaccination with Leishmania braziliensis Antigens.
abstract: Total antigens from Leishmania braziliensis promastigotes, solubilized with sodium cholate (dsLp), were formulated within ultradeformable nanovesicles (dsLp-ultradeformable archaeosomes, (dsLp-UDA), and dsLp-ultradeformable liposomes (dsLp-UDL)) and topically administered to Balb/c mice. Ultradeformable nanovesicles can penetrate the intact stratum corneum up to the viable epidermis, with no aid of classical permeation enhancers that can damage the barrier function of the skin. Briefly, 100 nm unilamellar dsLp-UDA (soybean phosphatidylcholine: Halorubrum tebenquichense total polar lipids (TPL): sodium cholate, 3:3:1 w:w) of -31.45 mV Z potential, containing 4.84 ± 0.53% w/w protein/lipid dsLp, 235 KPa Young modulus were prepared. In vitro, dsLp-UDA was extensively taken up by J774A1 and bone marrow derive cells, and the only that induced an immediate secretion of IL-6, IL-12p40 and TNF-α, followed by IL-1β, by J774A1 cells. Such extensive uptake is a key feature of UDA ascribed to the highly negatively charged archaeolipids of the TPL, which are recognized by a receptor specialized in uptake and not involved in downstream signaling. Despite dsLp alone was also immunostimulatory on J774A1 cells, applied twice a week on consecutive days along 7 weeks on Balb/c mice, it raised no measurable response unless associated to UDL or UDA. The highest systemic response, IgGa2 mediated, 1 log lower than im dsLp Al2O3, was elicited by dsLp-UDA. Such findings suggest that in vivo, UDL and UDA acted as penetration enhancers for dsLp, but only dsLp-UDA, owed to its pronounced uptake by APC, succeeded as topical adjuvants. The actual TPL composition, fully made of sn2,3 ether linked saturated archaeolipids, gives the UDA bilayer resistance against chemical, physical and enzymatic attacks that destroy ordinary phospholipids bilayers. Together, these properties make UDA a promising platform for topical drug targeted delivery and vaccination, that may be of help for countries with a deficient healthcare system.
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes. Roque Saenz Peña 352, Bernal, Argentina B1876BXD.
authors.forename: Leticia H
authors.initials: LH
authors.lastname: Higa
authors.affiliation: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata-CONICET, Sucursal 4 Casilla de Correo 16, 1900 La Plata, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Arnal
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires. Junin 956, 4° piso, 1113, Buenos Aires, Argentina.
authors.forename: Mónica
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes. Roque Saenz Peña 352, Bernal, Argentina B1876BXD.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Perez
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes. Roque Saenz Peña 352, Bernal, Argentina B1876BXD.
authors.forename: Priscila
authors.initials: P
authors.lastname: Schilrreff
authors.affiliation: Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mundiña-Weilenmann
authors.affiliation: Facultad de Ciencias Exactas, Centro de Investigación y Desarrollo de Fermentaciones Industriales (CINDEFI), UNLP. 50 No. 227, 1900 La Plata, Argentina.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Yantorno
authors.affiliation: Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata-CONICET, Sucursal 4 Casilla de Correo 16, 1900 La Plata, Argentina.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Vela
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes. Roque Saenz Peña 352, Bernal, Argentina B1876BXD.
authors.forename: María José
authors.initials: MJ
authors.lastname: Morilla
authors.affiliation: Nanomedicine Research Program, Departamento de Ciencia y Tecnologia, Universidad Nacional de Quilmes. Roque Saenz Peña 352, Bernal, Argentina B1876BXD.
authors.forename: Eder Lilia
authors.initials: EL
authors.lastname: Romero
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D055119:Elastic Modulus; D055352:Halorubrum / Q000737:chemistry; D006801:Humans; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology / Q000517:prevention & control*; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000008:administration & dosage*; D014611:Vaccination / Q000379:methods*
chemical_list: D000953:Antigens, Protozoan; D008081:Liposomes; D008563:Membrane Lipids; D016052:Protozoan Vaccines