Development of statin-loaded microneedle patch for anti-tumor immune modulation in melanoma

Summary: Introduction: Statins, established cholesterol-lowering drugs, are being investigated as anticancer agents and immune modulators. Cholesterol modulates several cellular functions e.g regulation of programmed death-ligand 1 (PD-L1) expression, checkpoint used by many cancers to evade immune surveillance. The goal of the study is to identify the dose of Simvastatin to modulate the function of macrophages and melanoma cells and to load in microneedle patches (MNPs) to target melanoma. Method: Mouse melanoma (B16F10, YUMM3.3) and macrophage cell lines were used for the study. PD-L1 expressions were assessed by flow cytometry and western blot techniques. Silicon molds (ST-07, array 8 × 8, height = 700 µm, base = 200 µm, pitch = 500 µm, shape = pyramid) were used to prepare MNPs. Statin-loaded MNPs were prepared by mixing simvastatin (20 mg/ml) with polymeric solution of chitosan (CS), polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) K30. Patches were characterized for chemical interactions (FTIR), tensile strength, elongation (%), and penetration capabilities using confocal microscopy. Loading efficiency was evaluated via HPLC. Result: Statins treatment significantly reduced PD-L1 expression in melanoma and macrophage cell lines dose-dependently. Macrophages showed higher sensitivity to statin-induced cell death and immune modulation. FTIR analysis demonstrated compatibility between statins and polymers with no direct interactions. MNPs exhibited optimal properties for transdermal delivery, including excellent tensile strength (103.021±2.06 mPa), elongation (42±1.414%), and penetration depth (430±46.05 µm). Conclusions: MNPs represent a promising platform for localized statin delivery as an immune modulator for melanoma. This approach circumvents rapid liver metabolism, minimizes systemic side effects, and enables sustained, controlled drug release. Additional <i>in-vitro</i> and mouse studies are ongoing to optimize statin-loaded MNPs as an adjuvant for melanoma immunotherapy. Riffat Latif¹, Hoe Kim², Hemachand Tummala¹ 1. Pharmaceutical Sciences, South Dakota State University, Brookings, SD, United States. 2. Seoul National University Cancer Research Institute, Seoul, Seoul, Korea (the Republic of). Pigmentation, Melanoma, and Melanoma Immune Surveillance