Mesoporous Materials: Synthesis And Application As Drug Carrier

Mesoporous material is a newly developed multidisciplinary research field initiatedin the early 1990s. It attracts wide interest of researchers because of its potentialapplications in catalysis, separation and drug delivery, etc, on the basis of its uniquecharacteristics, including homogeneous and controllable pore size within 2 to 50 nm, highspecific surface area and large pore volume. The mesostructure and chemicalcomposition of mesoporous material are its distinguishing features in differentapplications. Researchers tried to explain the formation mechanism and find controllingmethods of mesostructures from different perspectives, though not perfect to be appliedin most situations. In this paper, the anionic surfactant templating route to mesoporoussilica was focused on to advance the investigation of mesostructure formation, and a newreliable mechanism was proposed for the first time. We synthesized non-siliceous metaloxide mesoporous crystals by hard-templating method. And also in this work, a noveldrug delivery system was developed to make mesoporous silica applicable in transdermaldrug administration.In Chapter 2, a synthesis field diagram of anionic-surfactant-templated mesoporoussilica (AMS) was developed by using N-myristoyl-L-glutamic acid (C14GluA) astemplate and N-trimethoxylsilylpropyl-N,N,N-trimehylammonium chloride (TMAPS) asthe co-structure directing agent (CSDA), and varying the mole compositions of keycomponents in this system. By investigating the distribution of different phase zones inthe diagram, it was convinced that two mechanisms control the formation ofmesostructure. First, the pore geometry (bicontinuous, cylindrical and cage-type) iscontrolled by organic/inorganic interface curvature, which is dominated by surfactantpacking parameter g. Second, electrostatic interactions between mesocages play a vitalrole in their packing manners."Hard sphere packing"is applied if the electrostaticinteractions between mesocages are large enough, and in this case Fm-3m structure isfavored. Otherwise,"soft sphere packing"is applied and a compromise between"closepacking"and"minimum surface area"determines the final structure. In this case, Fd-3m and Pm-3n phases are favored when the electrostatic interactions between mesocages arerelatively small, and otherwise P42/mnm is favored. The second mechanism was proposedfor the first time.In Chapter 3, a thick-walled mesoporous silica was synthesized by a rational designof surfactant molecule. A fatty alcohol ether carboxylate surfactant (AEC) was used asthe template, and a double silica skeleton was formed by hydrogen bonding interactionsbetween polyethyloxide (PEO) and silica oligomers and electrostatic interactions betweencarboxylate and CSDA. An enhanced hydrothermal stability was proved by experimentbecause of the thick wall of the material. And its wall thickness was fine tuned by theaverage chain length of PEO in the AEC surfactant.In Chapter 4, cobalt oxide replicas of mesoporous silica SBA-15 (p6mm), KIT-6(Ia-3d) and AMS-10 (Pn-3m) with different pore sizes were synthesized by using hardtemplating method, and the relationship between pore size and symmetry of templatematerials and structure of cobalt oxide replicas was investigated systematically. (1)Separated single crystalline cobalt oxide fibers were obtained when the pore size ofSBA-15 was small, and mesoporous cobalt oxide was achieved retaining the originalsymmetry and morphology if the pore size of template material was large. (2) WhenKIT-6 was used as hard template for the synthesis of mesoporous cobalt oxide, bothreplication of one set and two sets of bicontinuous networks were observed if the poresize of KIT-6 was small. Otherwise, two interwoven networks of the Ia-3d structurewould be fully replicated by cobalt oxide when the pore size of KIT-6 is large. (3) Withinall available pore sizes (5.1-6.7 nm) of AMS-10, cobalt oxide replicated both one set andtwo sets of bicontinuous networks of Pn-3m structure. On the other hand, the structure ofreplica reflects the characters of model material, and it is reasonable that AMS-10 hasregular micropores at the thinnest part of the silica wall which grows following thediamond (D) minimal surface, connecting two interwoven mesopore networks.In Chapter 5, a potential transdermal drug delivery system was developed on thebasis of mesoporous materials. Fluorescein-5-isothiocyanate (FITC) was used as a drugmodel, which was conjugated to a cell-penetrating peptide (CPP) to make it capable oftranslocating membranes. The FITC-CPP conjugate was introduced into theorganic/inorganic hybrid mesostructured silica, which fulfilled the safety storage of thedrug and the control of the release rate. The effectiveness of this drug delivery system was proved by in-vitro release, matrix-assisted laser desorption/ionization–time of flightmass spectrometry (MALDI-TOFMS) and cell assay. The in-vitro release shows asigmoidal feature, including three steps: introduction, accelerated release and completingrelease. The typical duration is longer than 120 hours. When incubating the FITC-CPPloaded organic/inorganic hybrid mesostructured silica with DU145 cells, a sustainedinternalization of FITC-CPP by cells was observed, and FITC signals was well detectedafter as long as 96 hours. It means the organic/inorganic hybrid mesostructured silica iscapable of protecting drug-CPP from decomposition and controlling the drug release,which results in sustained cell internalization. This study shows that it could be apotential prototype for transdermal drug delivery system.