From tree to therapy: A critical review of Azadirachta indica microneedle patches in traumatic ulcer treatment

Background: Traumatic oral ulcers, arising from mechanical, thermal, or chemical insults, pose significant clinical challenges due to persistent pain, risk of secondary infection, and rapid clearance of topical therapies by saliva. Conventional treatments often require frequent reapplication and provide single‐mode pharmacology, limiting efficacy and patient compliance.

Objective: To evaluate the integration of Azadirachta indica (Neem) phytochemicals into dissolvable microneedle patches (MNPs) as a novel, multi‐modal delivery system for enhanced treatment of traumatic oral ulcers.

Methods: Review of literature from January 2015 to May 2025 was conducted across PubMed, Scopus, and Web of Science, focusing on Neem’s pharmacology and MNP design for oral mucosal applications. Key parameters extracted included phytochemical profiles, anti‐inflammatory and antimicrobial mechanisms, MNP fabrication materials and architectures, release kinetics, biocompatibility, and In vivo efficacy.

Results: Neem’s limonoids and flavonoids exhibit coordinated inhibition of COX/LOX pathways, suppression of NF-κB signaling, macrophage M1→M2 polarization, and free‐radical scavenging, resulting in reduced inflammation and pain. In vitro and ex vivo studies of dissolvable HA/PVP‐based MNPs demonstrate reproducible penetration of oral mucosa, biphasic release over 72 hours, and ≥4 log₁₀ CFU bacterial reduction. In rat models, Neem‐loaded MNPs achieved 70% ulcer area reduction by day 3 and >95% by day 7, outperforming corticosteroid gels, with histology confirming enhanced re-epithelialization and angiogenesis.

Conclusions: The combination of Neem’s multi‐targeted bioactivity with controlled, localized delivery via dissolvable MNPs offers a promising strategy for traumatic oral ulcer management. Future research should advance standardized MNP fabrication, optimize extract loading, and initiate clinical trials to validate safety and efficacy in humans.