The present disclosure details various lipids, compositions, and/or methods of optimized systems and delivery vehicles for the delivery of nucleic acid sequences, polypeptides or peptides for use in vaccinating against infectious agents.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R.sup.1 and R.sup.2 are, the same or different, alkenyl, etc, and X.sup.1 and X.sup.3 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X.sup.3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L.sup.3 is a single bond, etc, R.sup.3 is alkyl, etc, L.sup.1 and L.sup.2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like. ##STR00001##

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) (wherein: R.sup.1 and R.sup.2 are, the same or different, alkenyl, etc, and X.sup.1 and X.sup.3 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X.sup.3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L.sup.3 is a single bond, etc, R.sup.3 is alkyl, etc, L.sup.1 and L.sup.2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like. ##STR00001##

An ionic diol has formula wherein R.sup.1 represents an alkyl group having from 6 to 18 carbon atoms; R.sup.2 and R.sup.3 independently represent alkyl groups having from 1 to 4 carbon atoms; R.sup.4 represents an alkylene group having from 2 to 8 carbon atoms; and R.sup.5 represents an alkylene group having from 1 to 8 carbon atoms. Antistatic polymers are formed by copolymerization of monomers including a diisocyanate, an ionic diol, a polyether diol, and at least one non-ionic diols. Methods of making the antistatic polyurethanes are also disclosed.

##STR00001##

The present disclosure provides polyamine-fatty acid derived lipidoids (e.g., compounds of Formula (I) or (II)) and methods of preparing the lipidoids. A described lipidoid includes R—C(═O)—O— moieties (where R is a lipid moiety), which may be hydrolyzed into non-toxic fatty acids. Also provided are compositions including a described lipidoid and an agent (e.g., polynucleotide, small molecule, peptide, or protein). The present disclosure also provides methods, kits, and uses that involve the lipidoids or compositions for delivering an agent to a subject, tissue, or cell and/or for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases, respiratory diseases, painful conditions, psychiatric disorders, and metabolic disorders. ##STR00001##

The present disclosure provides polyamine-fatty acid derived lipidoids (e.g., compounds of Formula (I) or (II)) and methods of preparing the lipidoids. A described lipidoid includes R—C(═O)—O— moieties (where R is a lipid moiety), which may be hydrolyzed into non-toxic fatty acids. Also provided are compositions including a described lipidoid and an agent (e.g., polynucleotide, small molecule, peptide, or protein). The present disclosure also provides methods, kits, and uses that involve the lipidoids or compositions for delivering an agent to a subject, tissue, or cell and/or for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases, respiratory diseases, painful conditions, psychiatric disorders, and metabolic disorders. ##STR00001##

Provided herein are compounds, such as compounds of Formula (I), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, and isotopically labeled derivatives thereof, and compositions, methods, uses, and kits thereof. The compounds provided herein are lipids useful for delivery of polynucleotides, such as mRNA, for the treatment and/or prevention of various diseases and conditions (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, liver disease, spleen disease, lung disease, painful condition, psychiatric disorder, musculoskeletal disease, a metabolic disorder, inflammatory disease, or autoimmune disease).

Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.