Rapidly separable microneedle patch for the controlled and sustained release of 5-fluorouracil

5-Fluorouracil (5-FU) is frequently used in the treatment of tumors and swollen tissues. However, traditional administration methods can result in poor patient compliance and require to administrate frequently due to the short T1/2 of 5-FU. Herein, the 5-FU@ZIF-8 loaded nanocapsules were prepared using multiple emulsion solvent evaporation methods to enable the controlled and sustained release of 5-FU. To decrease the drug release rate and enhance patient compliance, the obtained pure nanocapsules were added to the matrix to fabricate rapidly separable microneedles (SMNs). The entrapment efficiency (EE%) of 5-FU@ZIF-8 loaded nanocapsules was in the range of 41.55-46.29 %, and the particle size of ZIF-8, 5-FU@ZIF-8, and 5-FU@ZIF-8 loaded nanocapsules were 60 nm, 110 nm, and 250 nm respectively. According to the release study in vivo and in vitro, we concluded that 5-FU@ZIF-8 nanocapsules could achieve the sustained release of 5-FU and that the burst release of nanocapsules could be elegantly handled by incorporating nanocapsules into the SMNs. What's more, the use of SMNs could improve patient compliance due to the rapid separation of needles and backing of SMNs. The pharmacodynamics study also revealed that the formulation would be a better choice for the treatment of scars due to the advantages of painlessness, separation ability, and high delivery efficiency. In conclusion, the SMNs containing 5-FU@ZIF-8 loaded nanocapsules could serve as a potential strategy for some skin diseases therapy with controlled and sustained drug release behavior.