Bilayer-Forming Synthetic Lipids: Drugs or Carriers?

Abstract

Since their introduction as bilayer-forming synthetic compounds in the eighties, dioctadecyldimethylammonium (DODA) and dihexadecylphosphate (DHP) salts have found many uses in strategic, applied areas. In particular, DODA chloride or bromide vesicles interacted with negatively charged prokaryotic or eukaryotic cells, yielding adsorption isotherms of high affinity for the cell surface, causing cell adhesion and flocculation, changing the cell surface charge from negative to positive, and causing loss of cell viability over DODA concentration ranges that depended on the cell type being tested. This work reviews data on DODA effects on cell viability (bacteria, fungus and cultured mammalian cells) to propose DODA salts as effective anti-microbial agents that exhibit differential cytotoxicity in vitro and, therefore, deserve to be investigated as potential drugs. The full utility of these inexpensive synthetic bilayers and bilayer fragments able to act as drugs themselves and, simultaneously, as drug, gene or vaccine carriers remains hitherto unexplored.

Lipid-based Biomimetics in Drug and Vaccine Delivery

“…Electrokinetic properties of the covered particles were very similar to those of vesicles; the mean-z-average diameter of particles in the latex/vesicle mixtures increased of 10 nm, consistently with the increase in diameter expected from deposition of one bilayer on the www.intechopen.com particles (Carmona-Ribeiro & Midmore, 1992). The interaction between lipids and particles has been reviewed over the last two decades in a few review articles and book chapters (Carmona-Ribeiro, 1992;Carmona-Ribeiro and Lessa, 1999;Carmona-Ribeiro, 2001 a,b;Carmona-Ribeiro, 2003;Carmona-Ribeiro et al, 2006;Carmona-Ribeiro, 2006;CarmonaRibeiro, 2007;Petri & Carmona-Ribeiro, 2007;Mamizuka & Carmona-Ribeiro, 2007) and lately other excellent reviews appeared in the literature (Bulte & De Cuyper, 2003;Troutier & Ladavière, 2007;Al-Jammal & Kostarelos). Figure 4 illustrated possible assemblies resulting from the interaction between bilayer-forming lipids and particles as depicted from experimental evidences (Carmona-Ribeiro & Midmore, 1992;Carmona-Ribeiro & Herrington, 1993;Rapuano & Carmona-Ribeiro, 1997;Carmona-Ribeiro & Lessa, 1999;Moura & Carmona-Ribeiro, 2003;Moura & Carmona-Ribeiro, 2005;Moura & Carmona-Ribeiro, 2007).…”

“…Absence of DODAB vesicle disruption upon interaction with the bacteria was depicted from absence of [ 14 C]-sucrose leakage from vesicles in experiments where this marker was used to label the inner water compartment of the vesicles (Martins et al, 1997). The differential cytotoxicity of DODAB lipid was illustrated in Table 2 (adapted from Carmona -Ribeiro, 2003;Carmona-Ribeiro, 2006;Mamizuka & Carmona-Ribeiro, 2007 In conjunction with amphotericin B, DODAB bilayer fragments provided a novel drug formulation with excellent activity against systemic candidiasis in mice (Vieira & CarmonaRibeiro, 2001;Lincopan et al 2003) but low nephrotoxicity (Lincopan et al, 2005) …”

“…Recently, the optimal bilayer coverage of polystyrene sulfate (PSS) nanoparticles with a cationic dioctadecyldimethylammonium bromide (DODAB) bilayer found an important application adsorbing and successfully presenting antigens to the immune system Lincopan et al, 2009a). From the literature, the potential of hybrid particle-lipid systems in diagnostics and therapeutics is starting to be realized (Carmona-Ribeiro, 2003;Katagiri et al, 2004;Pichot, 2004;Troutier et al 2005;Urban and Lestage, 2006;Al-Jamal and Kostarelos, 2007;Petri and Carmona-Ribeiro, 2007;Singh et al, 2008;Soo et al, 2009). Bilayer-coated or solid lipid nanoparticles have also been employed to formulate other drugs.…”

“…Sterically stabilized cisplatin nanocapsules containing 6 mol% DSPE-PEG served as the starting formulation for in vivo studies addressing the antitumor efficacy of cisplatin nanocapsules in tumor-bearing mice; there was a requirement of anionic phospholipid for successful nanoencapsulation of the cationic aqua-cisplatin (Velinova et al, 2004). DODAB or DHP bilayer fragments have been used to formulate hydrophobic drugs (Vieira & Carmona-Ribeiro, 2001;Pacheco & Carmona-Ribeiro, 2003;Lincopan et al, 2003;Carmona-Ribeiro, 2003;Lincopan & CarmonaRibeiro, 2006). Amphotericin B or miconazole were solubilized by bilayer fragments at low drug to lipid molar ratios (Vieira & Carmona-Ribeiro, 2001;Pacheco & Carmona-Ribeiro, 2003;Lincopan & Carmona-Ribeiro, 2003) whereas at high drug to lipid molar ratios, drug particles were covered with synthetic bilayers from DODAB or DHP bilayer fragments (Pacheco & Carmona-Ribeiro, 2003;.…”

“…Electrostatically driven bilayer coverage from bilayer fragments onto oppositely charged latex produced a highly homodisperse particulate for biomolecules adsorption (CarmonaRibeiro and Midmore, 1992;Carmona-Ribeiro, 2003;Pereira et al, 2004;Rosa et al, 2008). Polystyrene sulfate (PSS) particles which are anionic can be covered with single cationic DODAB bilayers forming biomimetic particles prone to be used for DNA, proteins or antigen immobilization .…”