Some embodiments pertain to nanoparticle-based compositions and their use in methods for the delivery of therapeutic agents to subjects. In some embodiments, the compositions are stable for prolonged periods of time and provide enhanced bioavailability.

Some embodiments pertain to nanoparticle-based compositions and their use in methods for the delivery of therapeutic agents to subjects. In some embodiments, the compositions are stable for prolonged periods of time and provide enhanced bioavailability.

An object of the present invention is to provide a lipid composition capable of achieving excellent nucleic acid delivery. According to the present invention, there is provided a lipid composition containing a lipid represented by Formula (1) or a salt thereof, a nucleic acid, at least one non-cationic lipid, and a lipid represented by R.sup.51-L-(OCH.sub.2CH.sub.2).sub.n—O-R.sup.52 (in the formula, R.sup.51 represents a hydrocarbon group having 6 to 30 carbon atoms, L represents —CO— or a single bond, R.sup.52 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and n represents an integer of 10 to 150).

##STR00001##

In the formula, each symbol means the definition described in the description.

An object of the present invention is to provide a lipid composition capable of achieving excellent nucleic acid delivery. According to the present invention, there is provided a lipid composition containing a lipid represented by Formula (1) or a salt thereof, a nucleic acid, at least one non-cationic lipid, and a lipid represented by R.sup.51-L-(OCH.sub.2CH.sub.2).sub.n—O-R.sup.52 (in the formula, R.sup.51 represents a hydrocarbon group having 6 to 30 carbon atoms, L represents —CO— or a single bond, R.sup.52 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and n represents an integer of 10 to 150).

##STR00001##

In the formula, each symbol means the definition described in the description.

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.

Provided herein are compounds and pharmaceutical compositions useful in modulating kinase activity, and related diseases. Also provided herein are methods of treating an eye disease or disorder in a subject. Also provided herein are methods of reducing intraocular pressure in a subject. Also provided herein are methods of modulating kinase activity in a cell. Also provided herein are methods of making the compounds provided herein, and compounds useful for the preparation of the compounds provided herein.

Compounds are provided having the following structure (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein G.sup.1, G.sup.1′, G.sup.2, G.sup.2′, G.sup.3, L.sup.1, L.sup.1′, L.sup.2, L.sup.2′, X, X′, Y and Y′ 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##

Compounds are provided having the following structure (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein G.sup.1, G.sup.1′, G.sup.2, G.sup.2′, G.sup.3, L.sup.1, L.sup.1′, L.sup.2, L.sup.2′, X, X′, Y and Y′ 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##