Formulated and/or co-formulated nanocarriers (e.g., LNPs and/or SLNPs) comprising AR Prodrugs and methods of making the nanocarriers are disclosed herein. The AR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit A2aR. The AR Prodrugs can be formulated and/or co-formulated into a nanocarrier to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.

The present invention provides methods comprising the in vivo delivery of small nucleic acid molecules capable of mediating RNA interference and reducing the expression of myostatin, wherein the small nucleic acid molecules are introduced to a subject by systemic administration. Specifically, the invention relates to methods comprising the in vivo delivery of short interfering nucleic acid (siNA) molecules that target a myostatin gene expressed by a subject, wherein the siNA molecule is conjugated to a lipophilic moiety, such as cholesterol. The myostatin siNA conjugates that are delivered as per the methods disclosed are useful to modulate the in vivo expression of myostatin, increase muscle mass and/or enhance muscle performance. Use of the disclosed methods is further indicated for treating musculoskeletal diseases or disorders and/or diseases or disorders that result in conditions in which muscle is adversely affected.

The invention relates to new cationic polymers conjugated with D-fructose, as a result of which they can selectively interact with specific structure elements on cell surfaces. The problem was that of creating novel, biocompatible, easy-to-produce, D-fructose-conjugated cationic polymers that have a higher selectivity with respect to certain cell types. To solve this problem, the invention proposes cationic polymers with covalently bonded D-fructose of general formula (I) with the following components: a) cationic polymer: macromolecular compounds of n repeat units with one or more positive charges; b) linker: a unit that links the cationic polymer with D-fructose or derivatives of D-fructose by means of any alkyl or aryl group, any alkenyl or alkinyl group, an ether, thioether or amine, an ester, amide or other carboxylic acid derivative, a heterocycle (e.g. triazole or m maleimide), a disulphide, an imine or an imide; c) D-fructose: one or more D-fructoses or D-fructose derivatives in an open-chain, furanoid or pyranoid structure, not glycosidically linked via one of the five possible carbon atoms (1, 3, 4, 5, 6).

Disclosed herein are nanoparticles comprising a lipid core comprising a sterol; and a complex comprising a cationic agent and a therapeutic agent, wherein the complex is encapsulated within the lipid core. Methods to produce the nanoparticle comprise: combining a cationic agent, a therapeutic agent, and a first water-immiscible solvent with a first aqueous solution, thereby forming a mixture comprising a complex comprising the cationic agent and the therapeutic agent; combining the mixture with a second waterim-miscible solvent, thereby forming an aqueous phase and an organic phase, and separating the organic phase comprising the complex; combining the organic phase comprising the complex with a sterol and a first water-miscible organic solvent; and dispersing the complex in a second aqueous solution to form a herein disclosed nanoparticle. Methods for treating a disease and for reducing nanoparticle burst rate are also disclosed.

Compounds are provided having the following structure (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein X, Y, L.sup.1, L.sup.2, L.sup.3, G.sup.1, G.sup.2 and G.sup.3 are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided. ##STR00001##

The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) Wherein R1 includes an amino group. These compounds are particularly useful in the formulation and in vivo and ex vivo delivery of nucleic acid and protein therapeutics for preparing and implementing T cell transfection, gene editing, cancer therapies, cancer prophylactics, and in the preparation of vaccines.

##STR00001##

Provided herein are methods and compositions for the delivery of a combination of oxiplatin and folinic acid to a cell, tissue, or physiological site. The compositions comprise delivery system complexes comprising liposomes encapsulating dihydrate(1,2-diaminocyclohexane)platinum(II)-folinic acid or delivery system complexes comprising a 5-fluorouracil active metabolite. Also provided herein are methods for the treatment of cancer, wherein the methods comprise administering the delivery system complexes comprising dihydrate(1,2-diaminocyclohexane)platinum(II)-folinic acid or delivery system complexes comprising a 5-fluorouracil active metabolite that have therapeutic activity against the cancer.

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 invention is directed to carrier systems comprising ether-lipids conjugated to one or more bioactive ligands and exposed on the surface of the carrier system for use in targeted delivery and/or antigen display systems. Optionally one or more further bioactive agents may be encapsulated or embedded within or attached to or adsorbed onto the carrier system. The present invention is further directed to methods of their preparation and their uses in medical applications, such as targeted delivery of bioactive agents to specific tissues or cells and antigen display systems for the study, diagnosis, and treatment of traits, diseases and conditions that respond to said bioactive agents.

A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.