Drug delivery system using hyaluronic acid-peptide conjugate micelle

A method of producing a drug-loaded, hyaluronic acid-peptide conjugate micelle, which comprises the steps of:

• reacting hyaluronic acid (HA) or its pharmaceutically acceptable salt with tetra-n-butyl ammonium hydroxide (TBA-OH) to prepare HA-TBA of Chemical Formula 1;
• preparing a water-insoluble peptide with a terminal amine group;
• reacting a carboxylic group of the prepared HA-TBA with the terminal amine group of the water-insoluble peptide in the presence of an organic solvent to prepare a hyaluronic acid-peptide conjugate micelle;
• and
• loading a water-insoluble drug into the prepared micelle:
• wherein n is an integer of 50 to 10,000, and the water-insoluble peptide is anti-Flt1 peptide that is an antagonist peptide against VEGFR1.

A drug delivery composition, comprising:

• a micelle consisting of a shell region comprising hyaluronic acid (HA) or its pharmaceutically acceptable salt, and a core region comprising a water-insoluble peptide with a terminal amine group, wherein the water-insoluble peptide is bound to said hyaluronic acid or its pharmaceutically acceptable salt;
• and
• a water-insoluble drug loaded inside the micelle,
• wherein the water-insoluble peptide is an antagonist peptide against VEGFR1 (anti-Flt1).