The pH sensitive archaeosomes (ApH) are multifunctional nanovesicles that offer a versatile platform for drug delivery because of their archaeolipids content. The ApH result from modifying a classical DOPE:CHEMS pH-sensitive nanoliposome, where DOPE is partly replaced by total polar achaeolipids. The archaeolipids are novel biomaterials extracted from a non-conventional (neither animal, vegetal not bacterial) source, the hyperhalophile archaebacteria Halorubrum tebenquichense. The presence of such archaeolipids, particularly of the majoritarian component 2,3-di-O-phytanyl-sn-glycero-1-phospho-(3'-sn-glycerol-1'-methyl phosphate (PGP-Me), renders the nanovesicles resistant to physical, chemical and enzymatic attacks, including to shear stress of nebulization. The PGP-Me is recognized as ligand of scavenger receptor Class A, ensuring thus macrophage targeting, making further covalent derivatization of nanovesicles unnecessary. Compared to nanoliposomes made of classical phospholipids extracted from plants, animals, or bacteria, the ApH provide massive cytoplasmic delivery of hydrophilic cargoes, as well as increased physical stability to storage and nebulization.
When nebulized across a pulmonary surfactant (PS) barrier, at least a fraction of nebulized ApH remained stable enough to execute higher cytoplasmic delivery in underlying cells. ApH would not induce biophysical changes leading to PS inactivation. Corticosteroids-loaded ApH are currently being explored as potent anti-inflammatory agents targeted to alveolar macrophages.