An annular corneal microneedle patch for minimally invasive ophthalmic drug delivery.

Microneedles directly penetrating into the cornea inevitably cause pain, corneal structure damage, and reduced light transmittance. In this work, a minimally invasive annular microneedle (A-MN) patch was developed avoiding direct puncture into the central cornea for ophthalmic drug delivery. The feasible mechanical strength of A-MNs was achieved by adjusting the ratio of PVP-β-CD and PVA to puncture the cornea barrier. Through effective diffusion to corneal stroma, bioavailability of hydrophilic small-molecule drugs, hydrophobic drugs, and macromolecular protein drugs through an A-MN patch was 24.36, 17.47, and 5.36 times higher than that of free drug administration. A-MNs effectively maintained light transmittance of the cornea with a light transmittance of 96.33 to 100%, which was higher than that of S-MNs. Furthermore, A-MNs effectively avoided corneal tissue and nerve damage along with the pain. The efficiency and safety of A-MNs were also examined through both an in vitro cell experiment and an in vivo animal experimental model, which showed great potential in clinical application.