Biodegradable multi-block copolymers of poly(amino acid)s and poly(ethylene glycol) for the delivery of bioactive agents
OwnerCheol-Hee Ahn, Su Young Chaeinventors
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Abstract
This patent discloses the synthesis of a multi-block copolymer containing poly(amino acids) (PAA) and a hydrophilic polymer which are degradable under physiological conditions. Control over the degradation rate of the obtained copolymers is achieved by introducing ester, amide or urethane groups as a biodegradable linkage connecting the PAA and the hydrophilic polymer. The biodegradable multi-block copolymers display high transfection efficiency in plasmid delivery with low cytotoxicity.
Claims35
A biodegradable multi-block copolymer comprising a poly(amino acid) (PAA), and a hydrophilic polymer, wherein the PAA is linked with the hydrophilic polymer by a biodegradable linkage.
A biodegradable multi-block copolymer comprising a poly(amino acid) (PAA) and polyethylene glycol (PEG), wherein the PAA is linked with a PEG by a biodegradable linkage selected from the group consisting of esters, amides, urethanes and carbonate.
A biodegradable multi-block copolymer represented by the formula:
- 2
- wherein n is an integer from 5 to 1,000, m is an integer from 10 to 500, x is an integer from 1 to 100, R′ represent a biodegradable linkage, and R represents the residual portion of an amino acid or derivatives thereof.
A composition for the safe and efficient delivery system of bioactive agents comprising a biodegradable multi-block copolymer capable of forming a stable complex with a bioactive agent, said biodegradable multi-block copolymer comprising a poly(amino acid) (PAA), and a hydrophilic polymer, wherein the PAA is linked with the hydrophilic polymer by a biodegradable linkage.
A composition for the safe and efficient delivery system of bioactive agents comprising a biodegradable multi-block copolymer capable of forming a stable complex with a bioactive agent, said biodegradable multi-block copolymer comprising a poly(amino acid) (PAA), and polyethylene glycol (PEG), wherein the PAA is linked with the hydrophilic polymer by a biodegradable linkage selected from the group consisting of ester, amide and urethane.
A transfection formulation comprising a biodegradable multi-block copolymer complexed with a selected nucleic acid in the proper charge ratio(positve charge of the copolymer/negative charge of the nucleic acid) that is optimally effective for both in vivo and in vitro transfection, said biodegradable multi-block copolymer comprising a poly(amino acid) (PAA), and a hydrophilic polymer, wherein the PAA has a high proportion of positively charged side groups and is a member selected from the group consisting of polylysine, polyarginine, block and graft copolymers thereof and activated derivatives thereof;
- and the PAA is linked with the hydrophilic polymer by a biodegradable linkage.
A method of transfecting a cell in vitro with biodegradable water soluble multi-block copolymers and a selected plasmid DNA, comprising the steps of:
- (a) providing a formulation comprising a biodegradable multi-block copolymer complexed with a selected nucleic acid in the proper charge ratio, said biodegradable multi-block copolymer comprising a poly(amino acid) (PAA), and a hydrophilic polymer, wherein the PAA has a high proportion of positively charged side groups and is a member selected from the group consisting of polylysine, polyarginine, block and graft copolymers thereof and activated derivatives thereof;
- and the PAA is linked with the hydrophilic polymer by a biodegradable linkage,
- (b) contacting the cell with an effective amount of the formulation such that the cell internalizes the selected nucleic acid;
- and
- (c) culturing the cell with the internalized selected plasmid DNA under conditions favorable for the growth thereof.
Dependencies are inferred from the claim text.