Variable pore size of mesoporous silica in improving physical stability and oral bioavailability of insoluble drugs

Mesoporous silica carriers are known to improve the solubility and bioavailability of poorly soluble Class II drugs. However, most mesoporous silica carriers available in the market have relatively low drug loading capacities. Therefore, it is essential to select the appropriate mesoporous silica carrier to control the particle size and form of poorly soluble drugs, as well as ensure efficient drug loading, particularly for drugs with large clinical dosages. In this study, three types of dendritic mesoporous silica nanoparticles (MSNs) with similar particle sizes but different pore sizes (25 nm, 15 nm, and 5 nm) were prepared, which could be degraded by 80 % in simulated intestinal fluid at pH 6.8 over 7 days. Fenofibrate (Fen) was loaded into MSNs, commercial mesoporous silica excipients, and a traditional solid dispersion excipient (PVP K-30) using the solvent evaporation method. MSNs showed a higher drug loading efficiency (about 33 %) compared to commercial excipients. The drug-loaded systems increased drug release rate and improved the hydrophilicity by reducing the contact angle. After loading, the specific surface area, pore volume, and pore size decreased. Under accelerated test condition, the rigid structure of MSNs prevented drug crystallization, avoiding the aging issues seen with traditional solid dispersions like PVP K-30, and improved the drug’s long-term stability. Pharmacokinetic studies in rats showed that the bioavailability of self-made Fen capsules was 1.31 times higher than that of commercial capsules (Lipanthyl®). In summary, these results highlighted the potential of MSNs to improve the stability and oral absorption of poorly soluble drugs.