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

Methods and compositions for inducing long-term tolerance by hybrid nanoparticles are provided. Compositions and formulations comprising hybrid nanoparticles with inherent affinity for innate immune cells are provided.

Disclosed herein are conjugates including a fatty acid, a self-assembly domain, and a polypeptide having phase transition behavior. Further disclosed are methods of using the conjugates to treat disease, methods of delivering an agent, and methods of preparing the conjugates.

Lipid-based delivery vehicles are provided. Nanoparticulate compositions typically including a p21 activated kinase (PAK) inhibitor and a lipid-based delivery vehicle are also provided. In preferred embodiments, the lipid-based delivery vehicle is a liposome, most preferably a sterically-stabilized liposome. Typically the lipid-based delivery vehicle includes one or more phospholipids, and optionally a sterol. In some embodiments, at least one of the phospholipids is PEGylated. In particular embodiments, the lipid-based delivery vehicle includes DSPC, DSPE-PEG2000, and cholesterol. In specific embodiments, the ratio of DSPC, DSPE-PEG, and cholesterol is 9:1:5. The nanoparticulate composition typically includes a PAK inhibitor, preferably a PAK-1 inhibitor such as IPA-3 or a derivative, prodrug, or pharmaceutically acceptable salt thereof. Methods of use, for example methods of treating cancer, particularly prostate and breast cancer by administering the composition to subjects in need thereof, are also provided.

Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)

##STR00001## wherein, A.sup.1 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.2 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A.sup.4 is proline; each A.sup.5 is independently selected from a natural or modified amino acid;
The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

The present disclosure is generally directed to spherical nucleic acids (SNAs) comprising multiple TLR agonists that enable the simultaneous activation of multiple TLR pathways for maximally synergistic immune activation. In some aspects, the present disclosure provides a spherical nucleic acid (SNA) comprising: (a) a nanoparticle core; (b) one or more toll-like receptor 3 (TLR3) agonists encapsulated in the nanoparticle core; and (c) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising one or more toll-like receptor 9 (TLR9) agonist oligonucleotides. Methods of using the SNAs are also provided herein.

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.

Lipid-based delivery vehicles are provided. Nanoparticulate compositions typically including a p21 activated kinase (PAK) inhibitor and a lipid-based delivery vehicle are also provided. In preferred embodiments, the lipid-based delivery vehicle is a liposome, most preferably a sterically-stabilized liposome. Typically the lipid-based delivery vehicle includes one or more phospholipids, and optionally a sterol. In some embodiments, at least one of the phospholipids is PEGylated. In particular embodiments, the lipid-based delivery vehicle includes DSPC, DSPE-PEG2000, and cholesterol. In specific embodiments, the ratio of DSPC, DSPE-PEG, and cholesterol is 9:1:5. The nanoparticulate composition typically includes a PAK inhibitor, preferably a PAK-1 inhibitor such as IPA-3 or a derivative, prodrug, or pharmaceutically acceptable salt thereof. Methods of use, for example methods of treating cancer, particularly prostate and breast cancer by administering the composition to subjects in need thereof, are also provided.

Nanoparticles include a polymeric core and a high density lipoprotein (HDL) component where the ratio by weight of the HDL component to the polymeric core is in a range from about 1:9 to about 9:1, such as about 75:25 or less or about 7:3 or less. The nanoparticles may also include a mitochondria targeting moiety. The nanoparticles may be used to treat or prevent atherosclerosis or to maintain lipid homeostasis.

The present disclosure relates to a reconstituted high density lipoprotein (rHDL) nanoparticle and a composition for preventing or treating a neurodegenerative disease comprising the same. Specifically, the present disclosure relates to a rHDL nanoparticle prepared by mixing a phospholipid and an apolipoprotein, and the rHDL nanoparticle of the present disclosure has amyloid-beta (Aβ) aggregation inhibitory effect.