Marina Biotech, Inc.

Novosom Ag

Novosom Verwaltungs Gmbh

Capsulution Pharma Ag

Silke Lutz

Steffen Panzner

Gerold Endert

Yvonne Kerwitz

Evgenios Siepi

Claudia Müller

Una Rauchhaus

Frank Essler

Cornelia Panzner

Christian Reinsch

Anja Behrens

Claudia Muller

Ute Vinzens

A serum-stable mixture of lipids capable of encapsulating an active agent to form a liposome, said mixture comprising phosphatidylcholine and phosphatidylethanolamine in a ratio in the range of about 0.5 to about 8. The mixture may also include pH sensitive anionic and cationic amphiphiles, such that the mixture is amphoteric, being negatively charged or neutral at pH 7.4 and positively charged at pH 4. Amphoteric liposomes comprising such a mixture may be used for encapsulating nucleic acid therapeutics, such as oligonucleotides and DNA plasmids. The drug/lipid ratio may be adjusted to target the liposomes to particular organs or other sites in the body.

Amphoteric liposomes

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.

Amphoteric liposomes, a method of formulating an amphoteric liposome and a method of loading an amphoteric liposome

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&#x2003;&#x2003;(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]&#x2003;&#x2003;(I).

Lipids and lipid assemblies comprising transfection enhancer elements

A method for the production of nano- or microcapsules having a diameter of from 20 nm to 40 &#x3bc;m is suggested, wherein template particles are supplied in an aqueous medium, electrically recharged with a polyelectrolyte, re-recharged without separation or washing steps using a second polyelectrolyte having a complementary charge with respect to the first polyelectrolyte, and said process is optionally continued with alternately charged polyelectrolytes.

Nanocapsules having a polyelectrolyte envelope

Growing community of inventors

Halle, Germany

Silke Lutz