The invention discloses a preparation method of a 
drug-loaded layer-by-layer self-
assembly coating. The preparation method comprises the following steps: A, performing aminating modification on 
hyaluronic acid by using 
dopamine; B, performing aminating modification on 
chitosan by using 3,4-dihydroxyl phenylpropionic acid; C, dissolving the 
dopamine in a trimethylol aminomethane solution with a PH value of 8.5 to form a 
mixed solution with 
dopamine concentration of 2mg / mL; soaking a matrix material in the 
mixed solution, reacting for time of t1 at a constant temperature, and washing the matrix material; D, preparing a modified 
hyaluronic acid solution with concentration of 2mg / mL and a PH value of 5.5, and dissolving a loaded 
drug into the modified 
hyaluronic acid solution to obtain a solution S1; preparing a modified 
chitosan solution with concentration of 2mg / mL, and dissolving the loaded 
drug to obtain a solution S2; soaking the matrix material obtained in step C into the solution S2 for a time of t2; then soaking in the solution S1 for a time of t3; and E, repeating the step D. The drug-loaded layer-by-layer self-
assembly coating has good PH response and stability and is suitable for the matrix materials of any shapes; and moreover, the preparation method has the advantages of simple operation, simpleness of needed equipment, low preparation cost and high applicability.