Dissolvable ulvan-based microneedles improve X-ray radiotherapy against skin cancer through local release of curcumin as a sensitizer

Abstract

Skin cancer frequently recurs after surgical excision, while conventional topical and systemic therapies are limited by poor delivery efficiency and systemic toxicity. To overcome these challenges, we developed a biocompatible, dissolvable microneedle (MN) system based on ulvan, a sulfated polysaccharide derived from Ulva lactuca, for localized intradermal delivery of curcumin micelles (Cur-m) to enhance X-ray radiosensitization. Cur-m was formulated via thin-film hydration using Pluronic P123, yielding uniformly distributed micelles (19.33 nm) with high encapsulation efficiency (98.27%) and drug loading (4.68 +/- 0.07%), enabling sustained drug release for up to 72 h. In vitro studies demonstrated potent cytotoxicity against melanoma (IC50 = 9.79 & micro;g/ mL) and human squamous cell carcinoma (IC50 = 1.59 & micro;g/mL). Notably, under 1.0 Gy X-ray irradiation, Cur-m exhibited a dose-dependent dual radiomodulatory effect, acting as a radioprotective agent at low concentrations (0.39 & micro;g/mL) and as a radiosensitizer at higher concentrations (1.56 & micro;g/mL). Cur-m was further incorporated into ulvan-based microneedles (Cur-UMN), achieving high insertion efficiency (99.56%) and rapid dissolution kinetics (43.02% within 30 s; 82.35% within 150 s). Franz diffusion studies confirmed efficient transdermal delivery, with 76.47% of Cur reaching the dermis within 4 h. In vivo IVIS imaging further validated precise, localized drug deposition. Collectively, this study presents a novel ulvan-based microneedle system integrating Cur micelles and radiotherapy, enabling minimally invasive, localized chemoradiotherapy with reduced systemic toxicity. This system offers a promising strategy to enhance radiosensitization while lowering both drug and radiation doses, addressing a critical unmet need in skin cancer treatment.