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.

Evidence of Skin Barrier Damage by Cyclic Siloxanes (Silicones)—Using Digital Holographic Microscopy

“…It should be emphasized that canyons have been so far only described in a few scientific manuscripts. They were indicated as an important, alternative pathway of diffusion of substances into the skin, including a transport route for dermal formulations in the form of nanoparticles [ 26 , 27 , 28 , 29 , 30 ]. Some studies have shown that canyons are characterized by limited resistance to penetration of xenobiotics applied to the skin [ 1 , 26 , 27 , 28 , 31 , 32 , 33 ].…”

Sulfated archaeal glycolipid archaeosomes as a safe and effective vaccine adjuvant for induction of cell-mediated immunity

“… 16 Furthermore, the addition of a detergent, sodium cholate, to TPL archaeosomes has been shown to generate ultradeformable archaeosomes (UDA) for topical delivery of vaccines to the skin. 19, 20 Nevertheless, despite these successes, the TPL archaeosome formulations typically used are relatively complex and comprise multiple lipid species. In attempts to overcome this, we have previously tested various semi-synthetic phospho-glyco-archaeol archaeosomes which offer some advantages over traditional TPL formulations while retaining adjuvanticity.…”

Transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination

“…The polar lipids in archaeosomes are responsible for the pronounced capture by phagocytic/immature APCs, resulting in strong CD4 + and CD8 + CTL responses to the entrapped antigens . The ultra‐deformable archaeosomes can penetrate the intact SC and reach the viable epidermis in the absence of classical permeation enhancers . Although no report is yet available on a genetic vaccine topically delivered by archaeosomes, the ultradeformable archaeosomes could be a promising platform.…”

“…86 The ultra-deformable archaeosomes can penetrate the intact SC and reach the viable epidermis in the absence of classical permeation enhancers. 87,88 Although no report is yet available on a genetic vaccine topically delivered by archaeosomes, the ultradeformable archaeosomes could be a promising platform.…”