Protective properties of mesocellular silica foams against aggregation and enzymatic hydrolysis of loaded proteins for oral protein delivery

Abstract

Numerous types of mesoporous silica nanoparticles (MSNs) have been studied as carriers for small molecular drugs. However, few reports have been conducted on small MSNs having large pores, and that are suitable for loading and orally delivering therapeutic proteins. In particular, their protective properties against aggregation and enzymatic hydrolysis of loaded proteins have been rarely studied. In this study, mesocellular silica foams (MCFs) with large and different pore sizes were prepared. The loading and release behaviors of three model proteins with different molecular weights were studied. The protective properties of the MCFs against enzymatic hydrolysis of the loaded proteins were tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography. The protecting effects of the MCFs against conformational change and aggregation of the loaded proteins were evaluated by circular dichroism and synchronous fluorescence spectra. Diabetic mice were inducted to evaluate in a preliminary manner the in vivo hypoglycemic effect of insulin loaded MCFs. The prepared MCFs showed rapid and high drug loading (up to 43%) of proteins. The release of proteins was tunable depending on the pore size. The lysozyme loaded MCFs could release 87% intact protein after incubation with pancreatin for 0.5 h. The digestion times for the insulin loaded in MCFs were prolonged to twice that of naked insulin. The secondary conformational changes for the insulin loaded in MCFs were only 1/40 to 1/20 of that of naked insulin incubated with Zn2+. Orally administered insulin-loaded MCF could reduce the blood glucose level to 69%. The prepared MCFs could effectively protect the loaded proteins from aggregation and enzymatic hydrolysis, thus exhibiting potential for application as carriers for protein delivery.