Biodegradable gelatin methacryloyl microneedles for transdermal nano-realgar administration in oral squamous cell carcinoma therapeutics

Oral squamous cell carcinoma (OSCC), the predominant malignancy in the head and neck region, poses a significant challenge with a high incidence and unfavorable prognosis, notwithstanding recent modest therapeutic advances. Biodegradable microneedles have emerged as a central focus for transdermal drug delivery, offering inherent advantages such as convenience, minimal invasiveness, negligible pain, cost-effectiveness, enhancement of drug delivery efficiency, and tunability. Nanosizing of realgar, particularly in the form of orpiment, enhances its solubility and bioavailability, thereby reducing the required dosage while mitigating inherent toxicity. In this study, we introduce an advanced drug carrier in the form of a biodegradable nanorealgar sustained-release microneedles (MNs) patch. Utilizing gelatin methacryloyl (GelMA) as the matrix material, hydrogel microneedles were meticulously fabricated and crosslinked via ultraviolet irradiation to modulate drug release, facilitating transdermal nano-realgar delivery for prolonged treatment of OSCC. This patch has features such as low toxicity, high selectivity, controlled drug release, no medical waste generation, and self-administration. Mechanical properties and drug release behavior of the microneedles were thoroughly investigated. In vivo experiments employing the oral squamous cell carcinoma cell line validated the remarkable therapeutic efficacy of nano-realgar-loaded GelMA MNs. This study represents a simple, safe, environmentally benign, and highly effective novel approach for the treatment of OSCC.