Drug-free hyaluronic acid-microneedle with unexpected inhibition activity on benzalkonium chloride-induced corneal inflammation and stromal scarring

Topical instilling of commercial artificial tears (cAT, containing 0.1 % hyaluronic acid) is widely employed to alleviate clinical manifestations of mild dry eye disease (DED) by preventing the pathological change of corneal epithelium. However, it showed limited therapy effectiveness on heavy DED which has further involved corneal stroma, due to its low stroma-available for hyaluronic acid (HA) resulting from the barrier of corneal epithelium. The present study developed a new microneedle-dosage form of cAT (cAT-MN). This cAT-MN can overstride the corneal epithelium and act as a long-lasting protective agent. Compared to cAT dosing (4 times/day), cAT-MN with one treatment exerted significantly higher therapeutic effects on curbing benzalkonium chloride (BAC)-induced corneal stroma scaring as well as alleviating the DED symptoms in the first 5-day BAC exposure; whereas, showed limited effects in a 10-day BAC exposure. To expand the therapy effects, MNs containing various amounts of HA were prepared. Thereinto, HA(6 %)-MN recovered corneal damage to healthy levels, which could be attributed to adding stroma-available for HA both by increasing the amounts of HA-delivery and enhancing HA-permeation. This study explores a new drug-free microneedle-dosage form of cAT to cure corneal stroma disorders which has expanded its indication, promising a wide clinical use in ophthalmology.