Formulation of Ferric metal-organic Frameworks Stabilized Sea Buckthorn oil-based Silymarin Incorporated Pickering Nanoemulsion for Oral Squamous Cell Carcinoma Treatment

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer globally, accounting for approximately 90% of all oral malignancies. Ferric-based metal-organic frameworks (Fe-BTC MOFs) have emerged as promising biomaterials due to their tunable surface properties, biocompatibility, and multifunctional applications in drug delivery, including customized release, intrinsic fluorescence, and ferroptosis induction. Silymarin (SL), a natural anticancer compound, exhibits therapeutic potential against oral cancer, while sea buckthorn (SB) oil serves as an effective lipid carrier for hydrophobic drugs. However, the poor aqueous solubility of SL limits its clinical efficacy. To overcome this challenge, we developed a Fe-BTC MOF-stabilized Pickering nanoemulsion (Fe-SB-SL-P-NEmul) for enhanced topical delivery in oral cavity anticancer therapy. The optimized Fe-SB-SL-P-NEmul exhibited excellent colloidal stability, with a zeta potential of -27.58 ± 2.24 mV and a nanometric particle size of 273.3 ± 9.5 nm. Comprehensive characterization through spectral, thermal, and morphological analyses confirmed successful drug encapsulation with high entrapment efficiency (92.69 ± 0.98%) and drug content (98.56 ± 0.87%). In vitro release studies demonstrated sustained drug release, with 92.12 ± 0.97% of SL released over 24 h at pH 6.8, following a diffusion-controlled mechanism. Additionally, the formulation exhibited significant anticancer activity against SCC-9 OSCC cells, likely due to the synergistic effects of SL, SB oil, and Fe-BTC MOFs-induced ferroptosis. Biocompatibility assessments further supported its safety profile. In conclusion, Fe-SB-SL-P-NEmul represents a novel, stable, and efficient nanocarrier system for the targeted delivery of SL in oral cancer therapy. Its ability to enhance drug solubility, modified release, and induce ferroptosis positions it as a promising candidate for future pharmaceutical applications.

Graphical Abstract