Nanostructures for the systemic delivery of nucleic acids, such as RNA, are provided herein. The nanostructures include templated lipoprotein nanoparticles (TLPs) composed of a core decorated with proteins, a lipid bilayer and hydrophobic molecules that self-assemble with nucleic acids, such as RNA. The nanostructures are useful for research, therapeutic and diagnostic applications.

The present invention is related to the field of targeted drug delivery. In particular, the particles and compositions described herein are used to deliver drugs to treat the diseases and conditions of interest. These particles and compositions include, but are not limited to, the lipopeptide complexes that mimic human high-density lipoproteins but contain apolipoprotein fragments or combination thereof.

[Problem] To provide: a lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration, contains a lipid that is bound to a peptide composed of multiple arginine residues as a constituent lipid, and includes a bacterial cell component having dispersibility in a non-polar solvent; and a method for producing a lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration and includes a substance of interest having dispersibility in a non-polar solvent. [Solution] A lipid membrane structure which has such a particle diameter that the lipid membrane structure can be sterilized by filtration, contains a lipid that is bound to a peptide composed of multiple arginine residues as a constituent lipid, and includes a bacterial cell component having dispersibility in a non-polar solvent.

The present invention is directed to a cargo-loaded cholesteryl ester nanoparticle with a hollow compartment (“cholestosome”) consisting essentially of at least one non-ionic cholesteryl ester and one or more encapsulated active molecules which cannot appreciably pass through an enterocyte membrane in the absence of said molecule being loaded into said cholestosome, the cholestosome having a neutral surface and having the ability to pass into enterocytes in the manner of orally absorbed nutrient lipids using cell pathways to reach the golgi apparatus. Pursuant to the present invention, the novel cargo loaded cholestosomes according to the present invention are capable of depositing active molecules within cells of a patient or subject and effecting therapy or diagnosis of the patient or subject.

The present invention provides stable, dry powder messenger RNA formulations for therapeutic use, and methods of making and using the same.

The invention relates to a process for preparing saposin lipoprotein particles, comprising a saposin-like protein, lipids and optionally a hydrophobic agent wherein the saposin-like protein or the hydrophobic agent is selectively bound to a support to allow the self-assembly of the saposin lipoprotein particles. The process of the invention comprises the step of a.) providing the hydrophobic agent and lipids, b. 1)/b.2 contacting the hydrophobic agent or the saposin-like protein with a support that is capable of selectively binding either of the two molecules to the support, c.1)/c.2) contacting the support-bound particle components with the remaining particle components, either the saposin-like protein or the hydrophobic agent, to allow for the self-assembly of the saposin lipoprotein particle on the support and d.) optionally eluting the support-bound saposin lipoprotein particles.

Disclosed herein are spherical high-density lipoprotein-like nanoparticles (HDL-NP) having a soft material core (e.g., a lipid-conjugated inorganic core). Also disclosed herein are methods for synthesizing the spherical HDL-NPs. Also disclosed herein are methods for treating disorders such as cardiovascular disease, cancer, inflammatory disorders or reducing NF-kB activity with the spherical HDL-NPs.

A reconstituted high density lipoprotein formulation having relatively low toxicity comprises an apolipoprotein such as ApoAI or fragment thereof, a lipid and a detergent at a level which is about 5-50% of that which would normally cause liver toxicity upon administration to a human. The lipid is optimally phosphatidylcholine at about 30-50 g/L and the molar ratio of apolipoprotein:lipid is optimally in the range 1:40 to 1:75. The formulation is useful for treating diseases or conditions such as cardiovascular disease, hypercholesterolaemia and hypocholesterolaemia inclusive of acute coronary syndrome (ACS), atherosclerosis and myocardial infarction.

A reconstituted high density lipoprotein formulation having relatively low toxicity comprises an apolipoprotein such as ApoAI or fragment thereof, a lipid and a detergent at a level which is about 5-50% of that which would normally cause liver toxicity upon administration to a human. The lipid is optimally phosphatidylcholine at about 30-50 g/L and the molar ratio of apolipoprotein:lipid is optimally in the range 1:40 to 1:75. The formulation is useful for treating diseases or conditions such as cardiovascular disease, hypercholesterolaemia and hypocholesterolaemia inclusive of acute coronary syndrome (ACS), atherosclerosis and myocardial infarction.

New proteophospholiposomes contain HDL-like vesicles with a new composite of anionic polypeptides, selected from the group of apoproteins A and at least one anionic polypeptide from the group of albumins, transthyretin-prealbumins and at least one cysteine group. The new anionic polypeptide composite is coated with layers of acyl-phosphatidylcholines that are protected from conversions by means of thio-phosphatidylcholines. The thiogroups attract antioxidants, ionic micromaterials and cofactors and are protected by exterior layers that contain neutral lipids and/or by means of capsules that contain microsomes, in an outwardly uniform fashion.