Sustained-release polymer micelle disruptable by HDL

A pharmaceutical composition comprising:

• a polymer micelle composition;
• and
• a drug encapsulated in the polymer micelle composition, the drug having a molecular weight of 1,500 or more and being selected from the group consisting of water-soluble physiologically active polypeptides and water-soluble physiologically active proteins,
• wherein:
• the polymer micelle composition comprises block copolymers each having a hydrophobic polymer chain segment and a hydrophilic polymer chain segment, a plurality of the block copolymers being arranged in a state in which the respective hydrophobic polymer chain segments are directed radially inward and the respective hydrophilic polymer chain segments are directed radially outward;
• at least some of the block copolymers have an affinity for HDL;
• a hydrophobic polymer chain segment of the block copolymers having an affinity for HDL comprises a polyamino acid including repeating units of a hydrophobic derivative of an amino acid, wherein the amino acid derivative comprises a side chain to which a sterol residue is covalently attached;
• the hydrophilic polymer chain segment of the block copolymer having affinity for HDL is comprised of poly(ethylene glycol);
• and
• detachment of the block copolymers having affinity for HDL is inducible by adhesion to HDL, such that at least one gap formed by the detached block copolymer(s) permits release of the encapsulated drug, which is not bound to the block copolymers, through the at least one gap.

A pharmaceutical composition, comprising:

• a polymer micelle composition;
• and
• a drug encapsulated in, but not bound to, the polymer micelle composition, the drug having a molecular weight of at least 1,500 and being a water-soluble, physiologically-active polypeptide or a water-soluble, physiologically-active protein,
• wherein:
• the polymer micelle composition comprises a plurality of block copolymers each having a hydrophobic polymer chain segment and a hydrophilic polymer chain segment, wherein the block copolymers are arranged such the respective hydrophobic polymer chain segments are located radially inward and the respective hydrophilic polymer chain segments are located radially outward;
• at least some of the block copolymers have an affinity for HDL;
• and
• the hydrophobic polymer chain segment of the block copolymers having an affinity for HDL comprises a polyamino acid including repeating units derived from a hydrophobic derivative of at least one amino acid having a side chain, the hydrophobic derivative formed by attachment of a sterol residue to the amino acid side chain.