In vitro evaluation of archaeosome vehicles for transdermal vaccine delivery

Abstract

Archaeosomes composed of archaeal total polar lipids (TPL) or semi-synthetic analog vesicles have been used as vaccine adjuvants and delivery systems in animal models for many years. Typically administered by intramuscular or subcutaneous injections, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses against entrapped antigens and provide protection in murine models of infectious disease and cancer. Herein, we evaluated various archaeosomes for transdermal delivery, since this route may help eliminate needle-stick injuries and needle re-use, and therefore increase patient compliance. Archaeosomes composed of TPL from different archaea (Halobacterium salinarum, Methanobrevibacter smithii, Haloferax volcanii) and various semi-synthetic glycolipid combinations were evaluated for their ability to diffuse across the skin barrier using an ex vivo pig skin model and the results were compared to conventional synthetic ester liposomes. Physicochemical characteristics were determined for selected formulations including vesicle size, size distribution, zeta potential, fluidity, antigen (ovalbumin) incorporation efficiency and release. Archaeosomes, in particular those composed of M. smithii TPL or the synthetic glycolipid sulfated S-lactosylarchaeol (SLA) mixed with uncharged glycolipid lactosyl archaeol (LA), appeared to be effective carriers for ovalbumin, achieving much better antigen distribution and vesicle accumulation in the skin epidermis than conventional liposomes. The enhanced skin permeation of archaeosomes may be attributed to their chemical structure and physicochemical properties such as particle size, surface charge, stability, and fluidity of their lipid bilayer.

Archaeosomes and Gas Vesicles as Tools for Vaccine Development

“…Similar results were obtained when influenza vaccine was used as antigen and administered topically in an archaeosome formulation, which also resulted in a strong IFN-g response (20). A comparison of archaeosomes composed of TPLs from three different archaea applied topically revealed differences in their ability of antigen distribution and vesicle accumulation in the skin epidermis (21). An archaeosome formulation containing total antigen extract from Leishmania braziliensis topically administered to mice induced a stronger antibody response to the L. braziliensis antigens than a lipid formulation, most likely because of its improved stability and uptake by APC (22).…”

Synthesis, characterization and kinetic study of silver and gold nanoparticles produced by the archaeon Haloferax volcanii

“…Halophilic organisms constitute a promising and relatively under-explored target for biotechnological applications due to the particular conditions their physiology requires (Singh and Singh 2017;Jia et al 2017;Haque et al 2019;Haque et al 2020). The halophilic archaeon Haloferax volcanii has become an important archaeal model system, as it is an organism that can be easily cultivated in the laboratory and for which many biochemical, molecular and genetic tools have been developed (Pohlschr€ oder and Schulze 2019).…”

“…Halophilic organisms constitute a promising and relatively under‐explored target for biotechnological applications due to the particular conditions their physiology requires (Singh and Singh 2017; Jia et al . 2017; Haque et al . 2019; Haque et al .…”

A Snapshot of Transdermal and Topical Drug Delivery Research in Canada

“…Using pig ear skin, the authors showed that all the tested particles generated from the total archaeal lipids had remarkably improved (up to 5 times) their capacity to cross the SC and deliver ovalbumin to the dermal layer compared to the liposomes composed of standard lipids or semi-synthetic glycosylarchaeol. While the authors observed that this improved permeability at least partially correlated with the fluid character of these archaeal vesicles, as well as with their negative surface charge, no other insights on the actual mechanism behind these activities has yet been provided [74]. While the small particle size is self-explanatory when it comes to permeation-enhancing properties of this system, a few previous works investigated similar systems for transdermal drug delivery applications and showed that their physical deformability is an important factor behind their significant SC permeability [75].…”