Archaeosomes based on novel synthetic tetraether-type lipids for the development of oral delivery systems

Abstract

The in vitro stability of archaeosomes made from novel synthetic membrane-spanning tetraether lipids was evaluated in conditions mimicking those of oral route application in terms of bile salts, serum and low pH..

Archaebacterial bipolar tetraether lipids: Physico-chemical and membrane properties

“…The neutral hydroxyl or lactosyl groups in the synthetic BTL are efficient stabilizing agents in the presence of bile salt-like detergents; and, lactose and phosphatidylcholine moieties enhance stability towards serum lipoproteins (Benvegnu et al, 2005). Lactose and mannose conjugated archaeosomes could be recognized by asialoglycoprotein receptors and mannose receptors (Benvegnu et al, 2005;Brard et al, 2007). Via receptor-mediated endocytosis, archaeosomes can be taken up by cells (Sprott et al, 2003).…”

“…A number of acyclic, macrocyclic and hemimacrocyclic tetraether lipids have been synthesized (Benvegnu et al, , 2005Brard et al, 2004Brard et al, , 2007Eguchi et al, 1998;Kim and Thompson, 1992;Nakamura et al, 2007;Thompson et al, 1992) (for a recent review, see Benvegnu et al, 2008;Jacquemet et al, 2009). Synthetic methods have been developed to incorporate cyclopentane rings into the isoprenoid chain, diacetylenic groups into the polymethylene units, and various polar headgroups to the synthetic tetraether lipid cores Brard et al, 2004Brard et al, , 2007Eguchi et al, 1998;Patwardhan and Thompson, 2000) and to create varying alkyl chain lengths in the hydrocarbon core region (Nakamura et al, 2007).…”

“…Moreover, liposomes made of synthetic BTL with various polar headgroups (including hydroxyl, lactose or phosphatidylcholine) (Benvegnu et al, 2005) and those made of total lipid extracts from archaea have shown stability properties under conditions encountered in the human gastrointestinal tract, which suggests that BTL-based liposomes have the potential as oral delivery systems (Benvegnu et al, 2005;Patel et al, 2000). The neutral hydroxyl or lactosyl groups in the synthetic BTL are efficient stabilizing agents in the presence of bile salt-like detergents; and, lactose and phosphatidylcholine moieties enhance stability towards serum lipoproteins (Benvegnu et al, 2005). Lactose and mannose conjugated archaeosomes could be recognized by asialoglycoprotein receptors and mannose receptors (Benvegnu et al, 2005;Brard et al, 2007).…”

The Headgroup (A)Symmetry Strongly Determines the Aggregation Behavior of Single-Chain Phenylene-Modified Bolalipids and Their Miscibility with Classical Phospholipids

“…This stabilizing approach was adopted from naturally occurring archaebacterial membrane lipids 4,25,26 and its applicability to drug delivery systems for pharmaceutical purposes was confirmed for a variety of natural and artificial bolalipids. [27][28][29][30][31][32][33][34] In our study we combine both, alkyl chain modifications and the introduction of headgroup asymmetry. At first, we synthesized two novel single-chain bolalipids, namely PC-C17pPhC17-PC and PC-C17pPhC17-OH.…”

Nature as a source of inspiration for cationic lipid synthesis

“…Moreover, bipolar archaeal lipids span the membrane from one side to the other constituting a single-layer membrane with a higher degree of physical rigidity than bilayer membranes. These features have been applied to design archaeal bipolar lipid analogues for lipoplex mediated gene delivery (Benvegnu et al 2005;Brard et al 2007). The dicationic glycine betaine-based tetraether GRcat 10 ( Fig.…”