MIL-100(Fe)-Enabled Oral Delivery of Syringic Acid with Enhanced Pharmacokinetics

Background/Objectives: Plant-derived bioactive compounds like syringic acid, a phenolic acid from the shikimic acid pathway, have shown potential against chronic diseases including diabetes, cardiovascular disorders, cancer, and cerebral ischemia. However, its poor water solubility and rapid systemic elimination result in low bioavailability, limiting therapeutic potential. This study aimed to enhance its bioavailability using MIL-100(Fe), a metal-organic framework (MOF) known for high surface area and drug-loading capacity. Methods: MIL-100(Fe) was synthesized using an optimized method and loaded with syringic acid through impregnation at 12, 24, 36, and 48 hours. Characterization included PXRD, FTIR, BET, SEM, and DLS. Acute oral toxicity was evaluated following OECD 425 guidelines, and bioavailability was assessed in Sprague Dawley rats. Results: The 1:2 syringic acid to MIL-100(Fe) ratio achieved the highest drug loading at 64.42 ± 0.03% (12 h). PXRD and FTIR confirmed successful loading (notably at 1242 cm⁻¹), and TGA indicated thermal stability at ~450 °C. SEM revealed octahedral particles with an average size of 270.67 ± 2.60 nm. BET showed reduced surface area post-loading. In vitro drug release exhibited media-dependent profiles. Toxicity tests indicated no adverse effects at 2000 mg/kg. Oral administration of SYA@MIL-100(Fe) resulted in a 10.997-fold increase in relative bioavailability versus oral syringic acid and 12.82-fold over intraperitoneal administration. Conclusions: MIL-100(Fe) is a safe and effective oral carrier for syringic acid, significantly enhancing its bioavailability. This platform shows strong potential for delivering phenolic compounds in pharmaceutical applications.