Methods and compositions for efficient delivery through multiple bio barriers
AssigneeCedars-Sinai Medical Center
InventorsEggehard Holler, Julia Y. Ljubimova, Keith L. Black
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Abstract
Mini nanodrugs that include a polymalic-based molecular scaffold with one or more peptides capable of crossing the blood-brain barrier, one or more plaque-binding peptides and one or more therapeutic agents attached to the scaffold are provided. Methods of treating brain diseases or abnormal conditions, and imaging of the same in a subject by administering the mini nanodrugs are described. Methods for reducing formation of amyloid plaques in the brain of a subject are disclosed.
Claims74
A mini nanodrug comprising:
- a polymalic acid-based molecular scaffold;
- at least one peptide capable of crossing the blood-brain barrier;
- at least one plaque-binding peptide;
- and
- an endosomolytic ligand;
- wherein
- each of the at least one peptide capable of crossing the blood-brain barrier, the at least one plaque-binding peptide and the endosomolytic ligand are covalently linked to the polymalic acid-based molecular scaffold, and
- the mini nanodrug ranges in size from 1 nm to 10 nm.
A mini nanodrug comprising:
- a polymalic acid-based molecular scaffold;
- at least one peptide capable of crossing the blood-brain barrier;
- an endosomolytic ligand;
- and
- a therapeutic agent, wherein
- each of the at least peptide capable of crossing the blood-brain barrier, the endosomolytic ligand and the therapeutic agent are covalently linked to the polymalic acid-based molecular scaffold, and
- the mini nanodrug ranges in size from 1 nm to 10 nm.
The mini nanodrug of claim 67, wherein the antibody is an IgG antibody or fragment thereof.
A method for treating a proliferative disease in a subject, comprising:
- administering a therapeutically effective amount of a mini nanodrug comprising a polymalic acid-based molecular scaffold, at least one peptide capable of crossing the blood-brain barrier, an endosomolytic ligand and an therapeutic agent to a subject in need thereof,
- wherein each of the at least peptide, the endosomolytic ligand and the therapeutic agent are covalently linked to the polymalic acid-based molecular scaffold, and the mini nanodrug ranges in size from 1 nm to 10 nm.
Dependencies are inferred from the claim text.