Bio-Inspired Polymeric Solid Lipid Nanoparticles for siRNA Delivery: Cytotoxicity and Cellular Uptake In Vitro

Abstract

Nanomedicine has introduced strategies that provide precise diagnosis and treatment with fewer side effects than traditional therapies. Treatments for neurodegenerative disorders, including Parkinson’s disease, are palliative, necessitating an innovative delivery system with a curative function. This study investigated a solid lipid nanoparticle (SLNP) system’s ability to bind and safely deliver siRNA in vitro. SLNPS were formulated using sphingomyelin and cholesterol, with Ginkgo biloba leaf extract (GBE) incorporated to enhance biocompatibility and neuroprotection. Poly-L-lysine (PLL) functionalization ensured successful siRNA binding, safe transport, and protection from nuclease degradation. SLNPs were physicochemically characterized, with binding and protection of siRNA assessed using agarose gels. Cytotoxicity, apoptotic induction, and cellular uptake studies were undertaken in the human neuroblastoma (SH-SY5Y) and embryonic kidney (HEK293) cells. The GBE-PLL-SLNPs had an average size of 93.2 nm and demonstrated enhanced binding and protection of the siRNA from enzyme digestion, with minimal cytotoxicity in HEK293 (<10%) and SH-SY5Y cells (<15%). Caspase 3/7 activity was significantly reduced in both cells, while efficient cellular uptake was noted. The present study provided a solid basis as a proof of principle study for future applications of the potential therapeutic in vitro, promising to address the unmet medical needs of patients with neurological disorders.