US 6,180,114 B2 · Therapeutic delivery using compounds self-assembled into high axial ratio microstructures

Abstract

Therapeutic complexes comprising plural therapeutic compounds self assembled into high axial ratio microstructures are described. The therapeutic complexes satisfy the formula HARM-Th, wherein HARM is a high axial ratio forming material and Th is a therapeutic coupled to or associated with the HARM. The therapeutic complexes also can satisfy the formula HARM-S-Th, wherein S is a spacer. Release of the therapeutic by the complex generally follows either 0-order kinetics or psuedo-first order kinetics. A method for delivering therapeutics to oransims, particularly humans, also is described. The method comprises administering an effective amount of (1) a ligand, such as a therapeutic, self-assembled into a HAR microstructure, or (2) a ligand, such as a therapeutic, coupled to or associated with a material capable of thereafter self-assembling into a high axial ratio microstructure, to the mammal. Nucleic acids are an example of a ligand that can be administered effectively according to this method through noncovalent attachment to the HARM-forming materials.

Claims71

Dependent claims

A complex self assembled into high axial ratio microstructures, the complex satisfying the formula HARM-Lg, where HARM is a high axial ratio microstructure forming material and Lg is a ligand noncovalently associated with the high axial ratio microstructure forming material, the HARM comprising less than 50 mole percent of a negatively charmed high axial ratio microstructure forming material.

A method for delivering a therapeutic complex to an organism, comprising:

providing a complex having a high axial ratio microstructure, the complex comprising nuclear or plasmid DNA noncovalently associated with a high axial ratio microstructure forming material, the high axial ratio microstructure forming material further comprising less than 50 mole percent of a negatively charged high axial ratio microstructure forming material;
and
administering an effective amount of the complex to the mammal.

A complex self assembled into high axial ratio microstructures, the complex satisfying the formula HARM-Lg, where Lg is a ligand noncovalently associated with a high axial ratio microstructure forming material and HARM is a high axial ratio microstructure forming material selected from the group consisting of amino-acid based amphiphiles, phospholipid-based amphiphiles, sphingosine based amphiphiles, aldonamide-based amphiphiles, and mixtures thereof, the amino-acid based amphiphiles satisfying a formula

where n=1-10, R1 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, R2 is H, R1 or R4, R3 is a functional group that allows noncovalent bonding of Lg to HARM, R4 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, W is O or S, X is O, S, NH, NR1, NR3 or NR4, Y is O or S, and Z is O, S, NH or NR1, the phospholipid-based amphiphiles satisfying the formula
where n=1-10, m=1-10, R1 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, R3 is a functional group that allows noncovalent bonding, of Lg to HARM, R4 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, W is O or S, X is O, S, NH, NR, NR3 or NR4, Y is O or S, and Z is O, S, NH or NR1, the sphingosine-based amphiphiles satisfying the formula
where n=1-10, m=1-10, R1 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, R3 is a functional group that allows noncovalent bonding of Lg to HARM, R4 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, X is O, S, NH, NR1, NR3 or NR4, and Y is O or S, and the aldonamide-based amphiphiles satisfying the formula
where R1 is an aromatic ring or rings, or an aliphatic organic or heteroaliphatic organic chain having from about 1-30 atoms, 0-6 sites of unsaturation and 0-6 heteroatoms, R2 is H or R1, and Y is O or S.

1 more element

A complex self assembled into high axial ratio microstructures, the complex satisfying the formula HARM-Lg and having a neutral or positive net charge, where HARM is a high axial ratio microstructure forming material and Lg is a nucleic acid ligand noncovalently associated with the high axial ratio microstructure forming material.

Dependencies are inferred from the claim text.

Therapeutic delivery using compounds self-assembled into high axial ratio microstructures

Life of this patent

Therapeutic delivery using compounds self-assembled into high axial ratio microstructures

Life of this patent

Abstract

Claims71