Surviving nebulization-induced Stress: Dexamethasone in pH-sensitive Archaeosomes

Abstract

DP-ApH suppressed IL-6 and TNF-α on phagocytic cells. Nebulized after 6-month storage, LpH increased size and completely lost its HPTS while ApH3 conserved size and polydispersity, fully retaining its original HPTS content.

Make It Simple: (SR-A1+TLR7) Macrophage Targeted NANOarchaeosomes

“…Opposingly, no differences in swelling diameter were observed between LIPO-IMQ+TLA and LIPO+IMQ+TLA. The low IMQ/PL ratio, much less extensive endocytic uptake of LIPO compared to ARC (Altube et al, 2016 ), together with the almost absent capacity of stimulating TNF-α and IL-6 on J774A.1 macrophages that rendered a less pronounced DTH on the other hand, suggested that only ARC but not LIPO, would succeed in modifying IMQ pharmacodynamics on target cells. Despite of not all immunogens inducing DTH are associated to a protective cell response (Nichols et al, 2002 ), a classical DTH reaction is considered indicative of cellular protective response (Crowle, 1975 ), mediated by T helper 1 (Th1) cells or activated CD4+ T cells (Cher and Mosmann, 1987 ) and CD8+ cytotoxic T cells (Kalish and Askenase, 1999 ).…”

“…Specifically, the polar archaeolipids extracted from Halorubrum tebenquichense , were identified by ESI-MS by Higa et al ( 2012 ) and ordered according to decrescent abundance as: archaeol analog methyl ester of phosphatidylglycerophosphate (PGPMe), archaeol analog phosphatidylglycerol (PG), (1-O-[α-D-mannose-(2′-SO3H)-(1′ α 2′)-α-D-glucose]-2,3-di-O-phytanyl-sn-glycerol) (SDGD5) the cardiolipin bis phosphatidylglycerol (BPG) and the glycocardiolipin SDGD5PA (2′-SO3H)-Manp-α1,2Glcpα-1-1-[sn-2,3-di-Ophytanylglycerol]-6-[phospho-sn-2,3-di-O-phytanylglycerol]. Recently the double negatively charged PGPMe, majoritarian polar lipid in H. tebenquichense responsible for its high negative Z potential of −40 mV, was confirmed to be a ligand of SRA-1 and not of SRB (the phosphatidylcholine receptor) (Altube et al, 2016 ).…”

“…Ligands internalization mediated by SR-A1 lacks- unless in case of stressed ER-, of negative feedback, being typically highly extensive (de Winther et al, 2000 ). Because of its content on SR-A1 ligand PGP-Me, nanovesicles and nanoparticles containing polar archaeolipids from H. tebenquichense experience extensive internalization as well, compared to the less pronounced of ordinary liposomes (Altube et al, 2016 ; Higa et al, 2017 ). Overall, the presence of these archaeolipids into otherwise labile nanovesicles not only avoids cumbersome chemical derivatization required for ligands linkage but provides nanovesicles with a higher tolerance to physicochemical stress (heat sterilization and storage under cold-free conditions, chemoenzymatic attacks (Caimi et al, 2017 ; Higa et al, 2017 ) than ordinary liposomes, constituting also an efficient mean to increase the intracellular delivery of loaded cargo.…”

Superoxide dismutase in nanoarchaeosomes for targeted delivery to inflammatory macrophages

“…Because of the ether linkages of archaeolipids, ARC are resistant to hydrolysis; the fully saturated isoprenoid chains of archaeolipids make ARC resistant to oxidation and the sn 2,3 stereoisomery of archaeolipids makes ARC resistant to stereospecific phospholipases [48]. Besides, the double negatively charged PGP-Me, majoritarian polar lipid of H. tebenquichense, responsible for the ARC high negative zeta potential (-40 mV), is a ligand of SRA1 [21]. SRA1 is a scavenger receptor expressed mainly in macrophages and dendritic cells [49][50][51], with broad ligand binding properties [52].…”

“…Archaebacterias on the other hand, are known to possesses archaeolipids, lipids having unique chemical nature made of saturated isoprenoid chains linked via ether bonds to the glycerol carbons at the sn 2,3 position. Different to liposomes prepared with phospholipids from plants or animal sources, ARC are colloidal and chemically resistant to different stress such as heat sterilization, storage under cold-free conditions [20] and nebulization [21]. Importantly, ARC are stable under GI conditions and efficiently protect encapsulated proteins from digestion [22]; concomitantly, shells made of archaeolipids layer protect solid lipid nanoparticles from lipolysis [23].…”