Microneedle patch-assisted transdermal administration of recombinant hirudin for the treatment of thrombotic diseases

The painless microneedle patch (MNP), widely explored for transdermal drug delivery of macromolecules, can overcome the limitations of traditional administrations of protein and polypeptide anticoagulant drugs. We constructed a recombinant hirudin-loaded microneedle patch, suitable for patients with thrombotic diseases requiring long-term preventive medication. The recombinant hirudin-loaded dissoluble microneedle patch (RHDMNP) was created using a mold casting technique and polyvinylpyrrolidone and polyvinyl alcohol were used as the matrix material with a 1:1.2 ratio. We prepared bilayer RHDMNPs with pyramidal appearance and 0.37 N/needle strength. The intradermal dissolution height of the microneedle reached approximately 78.67% of the total height, and 68.12% of the drug was delivered into the skin. The 12-hour cumulative permeation of the MNP was 21.69 +/- 3.90 mu g/cm2. The MNP showed a Tmax of 1.5 h, Cmax of 144 +/- 71 ng/mL, and area under curve (AUC) of 495 +/- 66 ng/mL.min compared to Tmax of 0.5 h, Cmax of 249 +/- 89 ng/mL, and AUC of 944 +/- 65 ng/ mL.min for the subcutaneous injection group. Both in vivo and in vitro experiments showed that the RHDMNP exerted effective anticoagulant effects, prevented the incidence of acute pulmonary embolism, and revealed the potential for venous thrombosis prevention.

Automated summary

The recombinant hirudin-loaded dissoluble microneedle patch demonstrated effective anticoagulant effects, prevented thrombotic diseases, and showed potential for preventing venous thrombosis.