The application discloses collagen nanospheres and a preparation method and application thereof. The preparation method comprises the following steps: 0.01-2wt% of collagen, 0.1-8wt% of
nucleic acid substances, 0.001-5wt% of positive electric substances, 0.1-7wt% of auxiliary agents and 78-99.78wt% of water are mixed according to the total
mass of the raw materials as 100wt%; the
nucleic acid substances are mixed with part of the water, and after high-pressure homogenization or microjet treatment, the
nucleic acid semi-
solid gel is obtained by low-temperature solidification, and the A phase is obtained by heating and melting; the collagen is dissolved in the A phase to obtain the B phase; the B phase and the C phase are mixed, and after high-pressure homogenization or microjet treatment, the auxiliary agent is added to form the collagen nanospheres; and the positive electric substances are dissolved in the residual water of the raw materials to obtain the C phase. The collagen nanospheres can improve the transmembrane transportation of the recombinant collagen and improve the
bioavailability, and meet the application requirements of the collagen nanospheres in transdermal
drug delivery products and the like.