Mesoporous Silica Nanoparticles: A Promising Inorganic Carrier for Solubility Enhancement

Abstract: Poor aqueous solubility remains a critical barrier to the development of orally administered drugs, particularly those in the Biopharmaceutics Classification System (BCS) Class II and IV. In recent years, Mesoporous Silica Materials (MSMs) have emerged as promising inorganic carriers for improving solubility and bioavailability. Their unique structural attributes, including high specific surface area, tunable pore sizes (2–50 nm), large pore volume, and abundant surface silanol groups, enable efficient drug adsorption, stabilization in the amorphous form, and prevention of recrystallization. Various synthesis methods such as sol–gel processing, liquid crystal templating, and microwave-assisted techniques allow precise control of pore architecture, while diverse drug-loading approaches (e.g., solvent evaporation, incipient wetness impregnation, co-milling, melt methods) enhance encapsulation efficiency and dissolution kinetics. Encapsulation within mesopores promotes spatial confinement and amorphization of poorly soluble drugs, significantly increasing dissolution rates and oral bioavailability. Functionalization of Mesoporous Silica Nanoparticles (MSNs) with hydrophilic groups or targeting ligands further improves wettability, dispersion, and site-specific delivery. Applications span the delivery of hydrophobic agents including fenofibrate, itraconazole, and carvedilol, with multiple-fold improvements in dissolution and therapeutic efficacy. Poor aqueous solubility remains a major limitation in the oral delivery of BCS class II and IV drugs. Mesoporous Silica Materials (MSMs) have emerged as versatile inorganic nanocarriers due to their high surface area, tunable pore architecture, and amenability to surface functionalization, enabling efficient drug loading, amorphization, and dissolution enhancement. This review uniquely integrates synthesis strategies, pharmaceutical optimization techniques, and biological performance under a unified framework, with particular emphasis on translational relevance. Recent advances in solvent-free loading, surface engineering, and stimuli-responsive systems are critically discussed alongside emerging in vivo pharmacokinetic, biodegradation, and toxicological evidence. Despite promising preclinical outcomes, challenges related to large-scale manufacturing, long-term biocompatibility, controlled clearance, and regulatory standardization remain. Addressing these gaps through biodegradable designs, rational particle engineering, and robust in vivo evaluation will be crucial for advancing mesoporous silica- based drug delivery systems toward clinical application.