Enzyme-responsive polymer peptide amphiphiles for targeted drug delivery to treat local and systemic inflammation

A method of preparing a micellar particle comprising a plurality of block copolymers, at least a portion, or each, of said block copolymers comprising at least one first block composed of a first plurality of backbone units covalently linked to one another and at least one second block of a second plurality of backbone units covalently linked to one another,

• wherein:
• the first block comprises at least one anti-inflammatory agent covalently attached, directly or via a linking moiety or group, to at least a portion of the first plurality of backbone units composing said first block;
• and
• the second block comprises at least one hydrophilic moiety covalently attached to at least a portion of the second plurality of backbone units composing said second block, said at least one hydrophilic moiety comprises an amino acid sequence that is capable of interacting with an inflammatory biomarker,
• and wherein the micellar particle comprises a core comprising said first block and a hydrophilic shell comprising said second block,
• the method comprising contacting the plurality of block copolymers with an aqueous solution.

A block copolymer comprising at least one first block composed of a first plurality of backbone units covalently linked to one another and at least one second block of a second plurality of backbone units covalently linked to one another,

• wherein:
• the first block comprises at least one anti-inflammatory agent covalently attached, directly or via a linking moiety or group, to at least a portion of the first plurality of backbone units composing said first block;
• and
• the second block comprises at least one hydrophilic moiety covalently attached to at least a portion of the second plurality of backbone units composing said second block, said at least one hydrophilic moiety comprises an amino acid sequence that is capable of interacting with an inflammatory biomarker.

A pharmaceutical composition comprising a micellar particle which comprises a block copolymer comprising at least one first block composed of a first plurality of backbone units covalently linked to one another and at least one second block of a second plurality of backbone units covalently linked to one another,

• wherein:
• the first block comprises at least one anti-inflammatory agent covalently attached, directly or via a linking moiety or group, to at least a portion of the first plurality of backbone units composing said first block;
• and
• the second block comprises at least one hydrophilic moiety covalently attached to at least a portion of the second plurality of backbone units composing said second block, said at least one hydrophilic moiety comprises an amino acid sequence that is capable of interacting with an inflammatory biomarker,
• and wherein the micellar particle comprises a core comprising said first block and a hydrophilic shell comprising said second block, the method comprising contacting the plurality of block copolymers with an aqueous solution,
• and a pharmaceutically acceptable carrier, the composition being formulated for local administration at or a in close vicinity to, an inflamed tissue in the subject.

A polymeric aggregate formed upon contacting a plurality of micellar particles with an inflammatory marker, wherein at least one of said micellar particles comprises a block copolymer comprising at least one first block composed of a first plurality of backbone units covalently linked to one another and at least one second block of a second plurality of backbone units covalently linked to one another,

• wherein:
• the first block comprises at least one anti-inflammatory agent covalently attached, directly or via a linking moiety or group, to at least a portion of the first plurality of backbone units composing said first block;
• and
• the second block comprises at least one hydrophilic moiety covalently attached to at least a portion of the second plurality of backbone units composing said second block, said at least one hydrophilic moiety comprises an amino acid sequence that is capable of interacting with an inflammatory biomarker,
• and wherein the micellar particle comprises a core comprising said first block and a hydrophilic shell comprising said second block.