Bilayer-Forming Synthetic Lipids: Drugs or Carriers? (original) (raw)
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Cationic Liposomes as Antimicrobial Agents
This document contains a mini-review of research work on bilayer-forming cationic lipids which selfassemble in water medium as closed bilayer membranes or liposomes and behave as very potent antimicrobial agents. In contrast to conventional liposomes, the large but differential cytotoxicity of cationic liposomes has been advantageously used against pathological microrganisms. This action has been described both in vitro against Gram-negative or positive bacterial strains and in vivo, against fungus. In certain instances, synergistic drug action against yeasts for fungicidal drugs carried by the antimicrobial bilayers has been described. Given the inexpensive character of certain synthetic cationic lipids and the multiple utility of liposomal models in drug delivery, many pharmaceutical applications are to be anticipated for this convenient joint venture.
Anais da Academia Brasileira de Ciências
Multiple uses for synthetic cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) bilayer vesicles are presented. Drugs or biomolecules can be solubilized or incorporated in the cationic bilayers. The cationic liposomes themselves can act as antimicrobial agents causing death of bacteria and fungi at concentrations that barely affect mammalian cells in culture. Silica particles or polystyrene microspheres can be functionalized by coverage with DODAB bilayers or phospholipid monolayers. Negatively charged antigenic proteins can be carried by the cationic liposomes which generate a remarkable immunoadjuvant action. Nucleotides or DNA can be physically adsorbed to the cationic liposomes to be transferred to mammalian cells for gene therapy. An overview of the interactions between DODAB vesicles and some biomolecules or drugs clearly points out their versatility for useful applications in a near future.
Cationic Vesicles as Bactericides
Langmuir, 1997
Dioctadecyldimethylammonium bromide (DODAB), a liposome-forming synthetic amphiphile, kills Escherichia coli, Salmonella thyphimurium, Pseudomonas aeruginosa, and Staphylococcus aureus in the micromolar range of DODAB concentrations. For the four species at cell concentrations higher than 10 7 bacteria/mL in the interaction mixtures, 5 µM DODAB, and 5 h of interaction time between bacteria and vesicles, 0% survival (no counts for viable cells) was obtained. The mechanism of cell death does not involve cell lysis or vesicle rupture as evaluated from measurements of cell leakage of phosphorylated compounds and from a vesicle disruption assay. The isolated external membrane of E. coli and DODAB cationic small vesicles do interact to yield an increase in the electrophoretic mobility of ghosts as a function of DODAB concentration. Surface charge for the ghosts becomes zero over the micromolar range of DODAB concentrations. Thus vesicle adhesion to the external membrane of the bacteria is certainly the first interaction step. Results on dose and time effects on cell viability generalize the bactericidal effect of cationic DODAB vesicles to four bacteria species of clinical importance. undergraduate fellowship. FAPESP and CNPq are gratefully acknowledged for research grants 96/0704-0 and 520186/96.6, respectively.
Lipid-based Biomimetics in Drug and Vaccine Delivery
InTech eBooks, 2010
Lipids provide adequate matrixes for supporting important biomolecules (proteins, DNA, oligonucleotides and polysaccharides) on model surfaces (latex, silica, silicon wafers, selfassembled monolayers, metals, polymers, insoluble drugs, biological cells and viruses). For example, biomolecular recognition between receptor and ligand can be isolated and reconstituted by means of receptor immobilization into supported lipidic bilayers on silica. This is an overview on novel lipid-based assemblies for drug and vaccine delivery. Especial emphasis will be on assemblies produced from the cationic, synthetic and unexpensive lipid dioctadecyldimethylammonium bromide (DODAB). DODAB vesicles interacted with negatively charged prokaryotic or eukaryotic cells with high affinity changing the cell surface charge from negative to positive and reducing cell viability. DODAB effects on cell viability (bacteria, fungus and cultured mammalian cells) revealed its high antimicrobial activity and differential cytotoxicity in vitro. DODAB bilayer fragments were combined with drugs, biomolecules or particles producing novel lipid-based biomimetics to deliver difficult drugs or design vaccines. Hydrophobic drug granules or aggregated recombinant antigens became well dispersed in water solution via lipid adsorption on drug particles as nanocapsules or protein adsorption onto supported DODAB bilayers. In other instances, hydrophobic drug molecules were attached as monomers to borders of lipid bilayer fragments yielding drug formulations effective in vivo at low drug-to-lipid-molar ratio. Cationic biomimetic particles from silica or latex covered with one cationic lipid bilayer proved effective for adsorption, presentation and targeting of biomolecules in vivo. Thereby antigens were effectively presented to the immune system by particles at defined and controllable sizes. The problem of delivering drugs, antigens or biomolecules to their targets in vivo is central and multidisciplinary and biomimetic assemblies are a major asset to improved and less toxic drug and vaccine delivery. Liposomes were first produced in 1965 by Alec Bangham in Cambridge UK and looked like myelin figures forming coherent and closed concentric spheroidal bilayers. From these early days up to the present, the development and diversification of the liposome "membrane" 25 www.intechopen.com
Langmuir, 2014
Supported lipid bilayers (SLBs) are simple and robust biomimics with controlled lipid composition that are widely used as models of both mammalian and bacterial membranes. However, the lipids typically used for SLB formation poorly resemble those of bacterial cell membranes due to the lack of available protocols to form SLBs using mixtures of lipids relevant for bacteria such as phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Although a few reports have been published recently on the formation of SLBs from Escherichia coli lipid extracts, a detailed understanding of these systems is challenging due to the complexity of the lipid composition in such natural extracts. Here, we present for the first time a simple and reliable protocol optimized to form high-quality SLBs using mixtures of PE and PG at compositions relevant for Gram-negative membranes. We show using neutron reflection and quartz microbalance not only that Ca 2+ ions and temperature are key parameters for successful bilayer deposition but also that mass transfer to the surface is a limiting factor. Continuous flow of the lipid suspension is thus crucial for obtaining full SLB coverage. We furthermore characterize the resulting bilayers and report structural parameters, for the first time for PE and PG mixtures, which are in good agreement with those reported earlier for pure POPE vesicles. With this protocol in place, more suitable and reproducible studies can be conducted to understand biomolecular processes occurring at cell membranes, for example, for testing specificities and to unravel the mechanism of interaction of antimicrobial peptides.
Langmuir
Cationic biocides have been widely used as active ingredients in personal care and healthcare products for infection control and wound treatment for a long time, but there are concerns over their cytotoxicity and antimicrobial resistance. Designed lipopeptides are potential candidates for alleviating these issues because of their mildness to mammalian host cells and their high efficacy against pathogenic microbial membranes. In this study, antimicrobial and cytotoxic properties of a de novo designed lipopeptide, CH 3 (CH 2) 12 CO-Lys-Lys-Gly-Gly-Ile-Ile-NH 2 (C 14 KKGGII), were assessed against that of two traditional cationic biocides C n TAB (n = 12 and 14), with different critical aggregation concentrations (CACs). C 14 KKGGII was shown to be more potent against both bacteria and fungi but milder to fibroblast host cells than the two biocides. Biophysical measurements mimicking the main features of microbial and host cell membranes were obtained for both lipid monolayer models using neutron reflection and small unilamellar vesicles (SUVs) using fluorescein leakage and zeta potential changes. The results revealed selective binding to anionic lipid membranes from the lipopeptide and in-membrane nanostructuring that is distinctly different from the co-assembly of the conventional C n TAB. Furthermore, C n TAB binding to the model membranes showed low selectivity, and its high cytotoxicity could be attributed to both membrane lysis and chemical toxicity. This work demonstrates the advantages of the lipopeptides and their potential for further development toward clinical application.
DOD/AMB: in vivo activity of a novel amb formulation with synthetic cationic bilayer fragments
Brazilian Journal of Microbiology, 2003
The ability of the versatile dioctadecyldimethylammonium bromide (DODAB), a bilayer-forming synthetic lipid previously shown to solubilize Amphotericin B (AMB), inspired this evaluation of in vivo activity of the DODAB/AMB formulation (DOD/AMB) against systemic candidiasis in a mouse model from survival and tissue burden experiments. AMB was simply added to a DODAB powder dispersion in water previously obtained by sonication with tip at concentrations ≤0.1 and 10 mg/mL, respectively, organic solvents completely absent. AMB aggregation state was evaluated from UV-visible light absorption and dynamic light scattering for aggregate sizing. AMB was stabilized by the DODAB bilayer fragments in its monomeric form, causing disappearance of large water insoluble drug aggregates. From survival and tissue burden experiments, DOD/ AMB efficacy was equivalent to the one exhibited by Fungizone (DOC/AMB) ---------100 and 70% survival respectively, at 0.4 mg/kg/day given i.p. for 10 days (P>0.05) ---------, regarding elimination of Candida colonization in spleen and kidneys. In summary, DOD/AMB, was effective for treating systemic candidiasis in a mouse model.
Interactions between cationic liposomes and drugs or biomolecules
Anais da Academia Brasileira de Ciências, 2000
Multiple uses for synthetic cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) bilayer vesicles are presented. Drugs or biomolecules can be solubilized or incorporated in the cationic bilayers. The cationic liposomes themselves can act as antimicrobial agents causing death of bacteria and fungi at concentrations that barely affect mammalian cells in culture. Silica particles or polystyrene microspheres can be functionalized by coverage with DODAB bilayers or phospholipid monolayers. Negatively charged antigenic proteins can be carried by the cationic liposomes which generate a remarkable immunoadjuvant action. Nucleotides or DNA can be physically adsorbed to the cationic liposomes to be transferred to mammalian cells for gene therapy. An overview of the interactions between DODAB vesicles and some biomolecules or drugs clearly points out their versatility for useful applications in a near future.
Bilayer vesicles and liposomes as interface agents
Chemical Society Reviews, 2001
Vesicles as interface agents flocculate or stabilize particulates, bacteria or mammalian cells. Synthetic cationic vesicles are antimicrobial agents killing bacteria and fungi at concentrations that barely affect cultured mammalian cells. Silica or latex become functional from coverage with bilayer-forming amphiphiles or phospholipids. Lipid selfassembly on particles allows receptor insertion and amplification of receptor-ligand recognition, e.g., model pair monosialoganglioside GM1 and its ligand, the cholera toxin.
Cationic surfactants and lipids as anti-infective agents
2006
Surfactants in general are well known for their ability of disrupting cell membranes and damaging microbes. However, cationic surfactants and lipids exhibit interesting additional properties because they can easily be targeted to oppositely charged biological structures such as cells or biomolecules of interest. This review emphasizes physicochemical and antimicrobial properties of cationic lipids and surfactants aiming at the establishment of structure-activity relationships. In special, cationic lipids forming bilayers revealed multiple abilities to carry antibiotics, drugs, genes, and antigens sometimes exhibiting synergic effects with the drug carried or displaying anti-infective properties by themselves.