Multi-Arm Polypeptide-Poly(ethylene glycol) Block Copolymers as Drug Delivery Vehicles
AssigneeNektar Therapeutics
InventorsXuan Zhao, Zhongxu Ren, Kazunori Emoto
Life of this patent
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Abstract
The invention provides a multi-arm block copolymer for use in delivering a variety of bioactive agents. The copolymer of the invention contains a central core from which extend multiple (3 or more) copolymer arms. Each copolymer arm possesses an inner polypeptide segment and an outer hydrophilic polymer segment. Thus, the overall structure of the copolymer comprises an inner core region that includes the central core and the inner polypeptide segment, while the outer core region is hydrophilic in nature. The multi-arm copolymer of the invention is particularly useful for delivery of biologically active agents that can be entrapped within the inner core region.
Claims26
A method comprising:
- (i) covalently attaching a polypeptide segment having a terminus to a central core molecule selected from the group consisting of glycerol, a reducing sugar, pentaerythritol, hydroxypropyl-β-cyclodextrin, and a glycerol oligomer, and wherein the central core molecule bears a hydrophilic ethylene glycol oligomer chain having a molecular weight of about 100 Da to about 5,000 Da;
- and
- (ii) covalently attaching a hydrophilic polymer segment to the terminus of the polypeptide segment, wherein the hydrophilic polymer segment (a) is selected from the group consisting of poly(alkylene glycols), copolymers of ethylene glycol and propylene glycol, poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxyalkylmethacrylamide), poly(hydroxyalkylmethacrylate), poly(saccharides), poly(a-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline and poly(N-acryloylmorpholine), (b) bears a capping group or a functional group selected from the group consisting of alkoxy, hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkyl or aryl sulfonate, halide, disulfide, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, hydrazide, thiol, carboxylic acid, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate and tresylate, to form a unimolecular multi-arm block copolymer having the structure:
- A(—O—B-L1-C)m′-(L2-D-E)n′
- wherein:
- A is a residue of the central core molecule;
- O is oxygen;
- B is the hydrophilic ethylene glycol oligomer chain;
- C is the polypeptide segment;
- D is the hydrophilic polymer segment;
- E is the capping group or functional group;
- L1 is a linkage between B and C formed from a chemical reaction;
- L2 is a linkage between C and D formed from a chemical reaction;
- (m′) is 3 to about 25;
- and
- (n′) is 2 to about 25, and (n′)≦(m′), wherein the unimolecular multi-arm block copolymer has a total molecular weight of about 10,000 Da to about 200,000 Da.
Dependencies are inferred from the claim text.