Abstract
PURPOSE: The purpose of this research was to study the basic physicochemical and biological properties regarding the application of L-tartaric acid modified chiral mesoporous silica nanoparticle (CMSN) as a drug carrier, and to explore the structure-property relationship of silica-based materials. METHODS: CMSN with functions of carboxyl modification and chirality was successfully synthesized through co-condensation method, and the basic characteristics of CMSN, including morphology, structure, wettability, degradation, bio-adhesion and retention ability in gastrointestinal tract (GI tract) were estimated by comparing with non-functionalized mesoporous silica nanoparticles (MSN). Meanwhile, the biocompatibility and toxicity of L-tartaric modification were systematically evaluated both in vitro and in vivo through MTT cell viability assay, cell cycle and apoptosis assay, hemolysis assay, histopathology examination, hematology analysis, and clinical chemistry examination. RESULTS: CMSN and MSN were spherical nanoparticles with uniform mesoporous structure. CMSN with smaller pore size and carboxyl functional groups exhibited better wettability. Besides, CMSN and MSN could dissolve thoroughly in simulated physiological fluids during a degradation period of 1-12 weeks. Interestingly, the in vitro and in vivo behaviors of carriers, including degradation, bio-adhesion and retention ability in the GI tract were closely related to wettability. As expected, CMSN had faster degradation rate, higher mucosa-adhesion ability, and longer retention time. Particularly, CMSN improved the bio-adhesion property in both gastric mucosa and small intestinal mucosa, and prolonged the GI tract retention time to at least 12 h, which meant higher probability for absorption. The biocompatibility and toxicity examination indicated that CMSN was a kind of biocompatible bio-material with good blood compatibility and negligible toxicity, which is required for further applications in biological fields. CONCLUSION: CMSN with functions of carboxyl modification and chirality had superiority in terms of both physicochemical and biological properties. The in vitro and in vivo behaviors of carriers, including degradation, bio-adhesion, and retention were closely related to wettability.