Enhancement of the solubility and antibacterial performance of rifaximin by loading on chitosan/PEG-functionalized mesoporous silica nanoparticles.

Antibiotics such as rifaximin (RFX) are hydrophobic compounds with poor aqueous solubility. Consequently, their therapeutic efficacy is often limited by low dissolution rates and poor bioavailability, despite their potent antimicrobial activity. This study aimed to enhance the solubility, stability, and bioavailability of RFX using chitosan/PEG-functionalized mesoporous silica nanoparticles (CP-MSNs) as a drug delivery system. CP-MSNs were synthesized via a sol-gel process, followed by functionalization with 3-aminopropyltrimethoxysilane (3-APTES) and electrostatic stabilization using chitosan and PEG. The RFX loading efficiency of the CP-MSNs exceeded 97%, which translates into a loading capacity of 38.8 mg g-1. CP-MSNs and RFX@CP-MSNs were characterized using UV-vis spectroscopy, a zeta sizer, field emission scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, and powder X-ray diffraction. The RFX@CP-MSNs exhibited sustained release of RFX, with a cumulative release of 88% at pH 5.5 and 83% at pH 7.4 over 48 h. The antibacterial activity of the RFX@CP-MSNs was evaluated against Staphylococcus aureus and compared with RFX in DI water. Although the initial MIC values were comparable, free RFX showed precipitation over time, leading to an increased MIC upon storage. In contrast, the RFX@CP-MSNs maintained stable MIC values for over six months, demonstrating improved long-term storage stability and highlighting the potential of CP-MSNs for delivering hydrophobic drugs.