Drug carrier with chelating complex micelles and the application thereof
Inventors
Wang, Chau-Hui • Chen, Chia-Hung • Lin, Johnson • Chen, Jing-Yi • Liao, Wei-Chuan
Assignees
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Publication Number
US-8785569-B2
Publication Date
2014-07-22
Expiration Date
Abstract
This invention provides Chelating Complex Micelles as a drug carrier. The Chelating Complex Micelles can load drugs without changing their structure, and therefore extend the half-life of drugs in the human body. The chelating complex micelles contain a metal ion core, at least one polymer, and at least one drug molecule. The metal ion is considered as a Lewis acid while polymer chain and drug molecules are referred to as Lewis bases. The drug molecule is linked to the polymer via forming coordinate bonds with metal ion, and then self-assembled to form chelating complex micelles as a drug carrier.
Core Innovation
The disclosed subject matter concerns chelating complex micelles (CCM) for carrying a Lewis base drug. The CCM drug carriers are formed by self-assembly of a Lewis acid metal ion core with Lewis base components, including a chelating polymer and the drug, via coordinate bonding.
The metal ion core is a ligand free Lewis acid and binds to the Lewis base polymer, and the metal ion core further links to the Lewis base drug via coordinate bonding. The approach addresses drug loading while not altering drug structure, with the goal of extending in vivo half-life.
The disclosure further describes specific embodiments and component selections, including metal ion cores such as Fe, Cu, Ni, In, Ca, Co, Cr, Gd, and others, together with Lewis base polymers including PEG-b-PGA and poly(glutamic acid) (PGA). An example embodiment describes a chelating complex micelle formed from PEG-b-PGA with FeCl2 and amifostine/WR-1065, and the disclosure also includes imaging-related metals such as Gd, Tc, Ga, Re, and In and mentions tumor targeting via incorporation of folic acid.
Claims Coverage
The independent claim defines a chelating complex micelle architecture with a ligand free Lewis acid metal ion core coordinate-bonded to a Lewis base polymer and coordinate-bonded to a Lewis base drug. Four inventive features are identified across the independent and dependent claims.
Chelating complex micelle architecture for carrying a Lewis base drug
A chelating complex micelle comprises a Lewis base polymer and a ligand free metal ion core selected from a group consisting of Fe, Cu, Ni, In, Ca, Co, Cr, Gd, Al, Sn, Zn, W, Sc, Ti, Mn, V, Mg, Be, La, Au, Ag, Cd, Hg, Pd, Re, Tc, Cs, Ra, Ir, Ga, wherein the metal ion core and the Lewis base polymers bind to each other by coordinate bonds, and wherein the metal ion core links to the Lewis base drug via coordinate bonding.
Ligand denticity class of Lewis base polymer
The chelating complex micelle further includes that the Lewis base polymer is selected from unidentate ligand, bidentate ligands, tridentate ligands, hexadentate ligands, and polydentate ligands.
Polymer molecular weight range
The chelating complex micelle includes a polymer having a molecular weight from 1,000 to 100,000 Daltons.
Copolymer of poly(ethylene glycol) and poly(glutamic acid)
The chelating complex micelle includes a copolymer of poly(ethylene glycol) and poly(glutamic acid).
Across the independent and dependent claims, the core inventive subject matter is a coordinate-bonded CCM that uses a ligand free Lewis acid metal ion core to bind a Lewis base polymer and coordinate-link the metal core to a Lewis base drug, while dependent claims refine the polymer ligand denticity, polymer molecular-weight range, and a specific PEG-b-PGA copolymer composition.
Stated Advantages
Extending in vivo half-life.
Drug loading without altering drug structure.
Documented Applications
Drug carriers for carrying Lewis base drugs, including cytoprotective agents such as amifostine and WR-1065.
Imaging applications using metals such as Gd, Tc, Ga, Re, and In.
Tumor targeting via folic acid incorporation.
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