Comparative Characterization and Evaluation of WS6 Loaded Nanoformulations Using Solid Lipid, PLGA, and PCL Versus Eudragit RS/RL Prepared by Microfluidics

Objectives: This study aimed to optimize WS6-loaded nanoparticles (NPs) with favorable therapeutic properties, including appropriate size, low toxicity, high encapsulation efficiency, and enhanced biocompatibility, for selective cancer targeting and regenerative applications. Methods: Three formulations were investigated: solid lipid nanoparticles (SLNs), polycaprolactone (PCL)-based NPs, and Eudragit RS100-based NPs via microfluidic synthesis. Their physicochemical properties were assessed, followed by biological evaluation on normal cells—dental-derived stem cells (DSCs), gingival fibroblasts (GFs), and human dermal fibroblasts (HDFs)—and cancer cell lines MDA-231 and HepG2. Assays included MTT for viability, apoptosis/necrosis, cell cycle analysis, ROS detection, and cytokine profiling. Results: SLNs showed inherent toxicity despite improved viability upon WS6 loading. PCL NPs improved encapsulation and compatibility but lacked stability. The microfluidic RS-WS6 NPs exhibited optimal characteristics, significantly enhancing viability in normal cells and selectively inducing apoptosis in cancer cells. At 1 µM, RS-WS6 NPs reduced ROS in normal cells (p < 0.05) and increased it in cancer cells (p < 0.05). Cytokine analysis revealed significant downregulation of IL-6, IL-12p70, and TNF-α (p < 0.05), indicating immunomodulatory potential. Conclusions: RS-WS6 NPs developed via microfluidics offer a promising therapeutic platform with selective cytotoxicity against cancer cells, minimal toxicity to normal cells, and anti-inflammatory properties, supporting their use in targeted therapy and regenerative medicine.