摘要:
Lipid assemblies, such as liposomes, comprising transfection enhancer elements (TEE's), which are complexed with the lipid assemblies by means of ionic interactions, or lipids incorporating such TEE's are disclosed for enhancing the fusogenicity of the lipid assemblies. The TEE's have the formula: hydrophobic moiety-pH sensitive hydrophilic moiety (II) The pH sensitive hydrophilic moiety of each TEE is a weak acid having a pka of between 2 and 6 or a zwitterionic structure comprising a combination of acidic groups with weak bases having a pKa of between 3 and 8. Lipids incorporating one or more such TEEs have the formula (I): Lipid moiety-[Hydrophobic moiety-pH sensitive hydrophilic moiety] (I)
摘要:
An amphoteric liposome comprising neutral lipids wherein said neutral lipids are selected from the group comprising cholesterol or mixtures of cholesterol and at least one neutral or zwitterionic lipid and wherein K (neutral) of said mixtures is 0.3 or less. Said amphoteric liposome may encapsulate an active agent, such as nucleic acid therapeutics. Also disclosed are pharmaceutical compositions comprising said amphoteric liposomes as a carrier for the delivery or targeted delivery of active agents or ingredients.
摘要:
An amphoteric liposome composed of a mixture of lipids, said mixture comprising a cationic amphiphile, an anionic amphiphile and optionally one or more neutral amphiphiles, at least one of said cationic and anionic amphiphiles being chargeable and the respective amounts of said cationic and anionic amphiphiles being selected such there is a stoichiometric excess of positively charged cationic amphiphile at a first lower pH, a stoichiometric excess of negatively charged anionic amphiphile at a second higher pH and said mixture has an isoelectric point intermediate said first and second pHs; characterised in that said positively charged cationic and negatively charged anionic amphiphiles are adapted to form a lipid salt with one another at said isoelectric point. Also disclosed are methods of predicting the fusogenicity of an amphoteric liposome at a given pH, formulating an amphoteric liposome and loading an amphoteric liposome with a cargo moiety.
摘要:
A method for preparing amphoteric liposomes loaded with polyanionic active agent as cargo, characterised by admixing an aqueous solution of said polyanionic active agent and an alcoholic solution of one or more amphiphiles and buffering said admixture to an acidic pH, said one or more amphiphiles being susceptible of forming amphoteric liposomes at said acidic pH, thereby to form such amphoteric liposomes in suspension encapsulating said active agent under conditions such that said liposomes form aggregates, and thereafter treating said suspension to dissociate said aggregates. Also disclosed are nucleic acid loaded amphoteric liposomes produced in accordance with the method, wherein said nucleic acids are oligonucleotides and said liposomes are multilamellar.
摘要:
A process for the preparation of compounds of the formula ##STR1## wherein the substituents X, Y and Z have the meaning given in the description, by reaction of compounds of the formula ##STR2## with a cyanide and an oxidizing agent other than Br.sub.2 in the presence of halides which offers industrial hygiene advantages and renders possible large-scale industrial access to dyestuff syntheses has been found.
摘要:
The present invention relates to methods for identifying and/or detecting T-cell epitopes of a protein antigen, to methods for preparing peptide vaccines against a protein antigen, to methods for controlling the quality of receptor/ligand complexes and/or their components, to methods for preparing nanoparticles having at least one immobilized receptor unit or an immobilized receptor, to methods for preparing nanoparticles having immobilized receptor/ligand complexes, in particular peptide-presenting MHC molecules, to methods for enriching and/or isolating specific CD4+-T- or CD8+-T-lymphocytes from peripheral blood mononuclear cells, to methods for priming a CD8+-T-lymphocyte reaction in vitro, to nanoparticles having an immobilized receptor unit, in particular an immobilized chain of an MHC molecule, to nanoparticles having an immobilized receptor, in particular an immobilized MHC molecule, to nanoparticles having an immobilized receptor/ligand complex, in particular a peptide-presenting MHC molecule, to a peptide vaccine, to a kit for identifying and/or detecting T-cell epitopes of a protein antigen, and to the use of the nanoparticles for identifying and/or detecting T-cell epitopes, for preparing peptide vaccines, for enriching and/or isolating specific T-lymphocytes and for priming a CD8+-T-lymphocyte reaction in vitro.