Valeriana wallichii-loaded tin oxide nanoparticle gel for targeted melanoma therapy: cytotoxicity, antioxidant activity, and cellular uptake evaluation.

The present study reports the formulation, characterization, and evaluation of a novel Valeriana wallichii-loaded tin oxide nanoparticle (V. wallichii-SnO₂-NPs) gel for targeted melanoma therapy. Using an eco-friendly synthesis approach, V. wallichii extract was encapsulated into SnO₂ nanoparticles and incorporated into a topical gel system. RP-HPLC analysis confirmed the presence and quantification of chlorogenic acid (CA) and quinic acid (QA) as marker constituents in the nanoparticle matrix, ensuring chemical consistency and bioactive retention post-formulation. The nanoparticles exhibited favorable physicochemical characteristics-mean particle size (∼75.1 nm), PDI (0.25), zeta potential (-29.4 mV), and high entrapment efficiency (CA: 83.67%; QA: 87.23%). Antioxidant activity assessed via DPPH assay demonstrated a high radical scavenging potential (87.14 ± 2.25%), supporting enhanced antioxidant properties upon nanoencapsulation. In vitro cytotoxicity was evaluated on A375 human malignant melanoma cells using the MTT assay, with dabrafenib-a clinically approved BRAF inhibitor-employed as a reference control. The nanoformulation exhibited dose-dependent cytotoxicity with an IC₅₀ value of 138.6 μg/mL, significantly outperforming the blank SnO₂-gel control. Confocal microscopy using DAPI and Rh123 dual staining confirmed enhanced mitochondrial uptake and intracellular localization in nanoparticles-gel treated cells (∼4.7 a.u.), compared to dabrafenib (∼3.3 a.u.) and untreated controls (∼1.7 a.u.). Stability testing under ICH Q1A(R2) conditions for 60 days revealed minimal variation in key parameters, ensuring long-term physicochemical resilience. Collectively, these findings establish the V. wallichii-SnO₂-NPs-loaded gel as a promising phytochemical-based nanotherapeutic with excellent cytocompatibility, intracellular delivery, and oxidative stress modulation-positioning it as a strong candidate for advanced melanoma treatment.