Method for manufacturing transdermally delivered hyaluronic acid-protein conjugate and transdermally delivered hyaluronic acid-protein conjugate manufactured using same

A method of transdermal delivery for a protein comprising:

• administering a hyaluronic acid-protein conjugate which is represented by having Chemical formula 2 to a subject in need thereof:
• in chemical formula 2,
• P is a water-soluble protein,
• the sum of m, n, and l is an integer of 50 to 10,000,
• the sum of n and l is an integer of 5 to 5,000, and
• l is an integer of 1 to 100,
• wherein the hyaluronic acid-protein conjugate is obtained by reacting the hyaluronic acid-aldehyde(HA-aldehyde) compound represented by Chemical formula 1 with N-terminus of a water-soluble protein:
• in chemical formula 1, the sum of m and n is an integer of 50 to 10,000, and n is an integer of 5 to 5,000, and the hyaluronic acid-aldehyde compound has a aldehyde substitution degree of 10 to 50 mole %;
• and
• the hyaluronic acid-protein conjugate includes 1 to 10 molecules of protein bound to a molecule of the hyaluronic acid-aldehyde compound,
• wherein the water-soluble protein is human growth hormone, erythropoietin, Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or ovalbumin,
• wherein blood is collected from the subject and blood concentration of the hyaluronic acid-protein conjugate is determined and the transdermal delivery has 20% bioavailability compared to a subcutaneous injection.