Published Paper Details:

Conventional chemotherapy is frequently hampered by a lack of tumor selectivity, resulting in systemic toxicity and a narrow therapeutic window. To address these limitations, this study reports the design, synthesis, and evaluation of actively targeted solid lipid nanoparticles (SLNs) for the enhanced delivery of paclitaxel (PTX). A series of PTX-loaded SLNs were developed and surface-functionalized with folic acid (FA) as a targeting ligand. The formulations included SLNs with FA conjugated directly to the surface (SLNFA) and SLNs with FA attached via polyethylene glycol (PEG) spacers of two different molecular weights, 1000 Da (SLNP1FA) and 4000 Da (SLNP4FA). Physicochemical characterization revealed that surface modification progressively increased particle size while maintaining a narrow distribution, and significantly enhanced drug entrapment. The SLNP4FA formulation demonstrated the highest drug entrapment efficiency at 58.22% and exhibited the most sustained in vitro drug release profile over 48 hours. The therapeutic efficacy of the nanocarriers was assessed against folate receptor (FR)-positive MCF-7 human breast cancer cells. All folate-targeted formulations showed superior cytotoxicity compared to free PTX and non-targeted SLNs. Crucially, the efficacy was dependent on the PEG spacer length, with SLNP4FA exhibiting the highest potency. This formulation achieved an IC50 value of 331.29 nM, representing a 48.39% reduction in the IC50 compared to free PTX. These findings demonstrate that optimizing the PEG spacer length is a critical strategy for overcoming steric hindrance and maximizing receptor-mediated endocytosis. The FA-PEG (4000)-SLN architecture represents a highly effective and promising platform for the targeted delivery of chemotherapeutic agents to solid tumors.