Ultradeformable archaeosomes as new topical adjuvants

Ultradeformable archaeosomes (UDA) are vesicles made of soybean phosphatidylcholine (SPC), sodium cholate (NaChol) and polar lipids from Halorubrum tebenquichense (3:1:3 wt/wt). Although ultradeformable liposomes (UDL, made of SPC and NaChol at 6:1 wt/wt) and UDA were neither captured nor caused cytotoxicity on keratinocytes, UDA was avidly captured by macrophages, their viability being reduced by 0.4-1.6 mg/mL phospholipids by 25 to 60%. Instead, UDL were poorly captured and caused no toxicity. Balb/C mice immunized by the topical route with four doses of ovalbumin (OVA)-loaded UDA, at 75 μg OVA/600 μg phospholipids (125 nm mean size and -42 mV zeta potential), induced IgG titers tenfold to 100-fold higher than those immunized with OVA-loaded UDL at the same dosage. Both matrices penetrate to the same skin depth (nearly 10 μm after 1 hour on excised human skin), being the higher topical adjuvancy and higher phagocytic uptake of UDA related to its glycolipid content.From the Clinical EditorThis work summarizes key findings related to the development of ultradeformable archaeosomes as vehicles utilized in transdermal delivery systems with improved skin penetration.

Graphical AbstractA. Comparative skin penetration of OVA-UDA with that of OVA-UDL, OVA-L, and OVA-ARC. In spite of penetrating to comparable depth, OVA-UDA was more efficiently taken up by skin APC than OVA-UDL, and this could be related to their capacity to induce higher anti-OVA IgG serum titers. The non-ultradeformable OVA-L and OVA-ARC did not trigger systemic titers by topical route probably because of their impaired skin penetration.B. Serum IgG titers after topical OVA-UDA, in comparison with topical OVA-UDL, OVA-L, OVA-ARC, subcutaneous OVA-UDA, and intramuscular alum-adsorbed OVA.Figure optionsDownload high-quality image (137 K)Download as PowerPoint slide