Keratin Microneedle Patches With Hop Extract For Oral Ulcers

This study aimed to develop a keratin-based microneedle patch loaded with hop extract (KMNs@HE) to overcome limitations of current oral ulcer therapies, such as short retention time and poor drug penetration (C. Vitamia, G.N. Iftinan, I.R. Latarissa, et al. Drug Des Devel Ther, 2024,18:1297 - 1312.). Eight-week-old male Sprague-Dawley rats (approved by Ethics Committee, No. QYFY WZLL 27832) with induced oral ulcers were divided into control (CON), keratin-only microneedle (KMNs), KMNs@HE, and commercial chitosan film (CTS) groups. Methods included antimicrobial/antioxidant assays, cytotoxicity testing (CCK-8 on L929 fibroblasts), microneedle characterization (SEM, mechanical tests), histopathology (HE, Masson, Sirius Red), and immunohistochemistry (CK5, CK13, TNF-α, IL-6). The 1000 μg/mL hop extract exhibited potent antimicrobial activity (100% inhibition at 12 h), high antioxidant capacity (DPPH: 90%, ABTS: 96%), and biocompatibility (cell viability >70%). KMNs@HE demonstrated sustained drug release (50% in 2 h, full release in 12 h), robust mechanical strength (120 N), and effective mucosal penetration (500 μm depth). In vivo, KMNs@HE achieved 85% ulcer closure by day 5 (P = 0.0184 vs. CTS), complete healing by day 7 (P < 0.001 vs. CON/KMNs), enhanced collagen regeneration, and reduced inflammatory markers (IL-6, TNF-α). KMNs@HE offers a pain-free, sustained-release system with superior healing efficacy and biocompatibility, positioning it as a promising alternative for oral ulcer therapy.