Effect of Surface Property on the Release and Oral Absorption of Solid Sirolimus-Containing Self-microemulsifying Drug Delivery System

Abstract

The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (Cmax) and the area under the concentration-time curve (AUC0→48). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15. Graphical abstract: [Figure not available: see fulltext.].