Research On The Preparation And Characterization Of Mesoporous Bioactive Glasses For Drug And Gene Delivery System

Mesoporous materials can be used as drug and bioactive factor delivery system becauseof their high surface area, ordered pore structure, narrow and tunable pore size distribution,which also show important research and application value in the field of biomaterials. Theresearch is mainly focus on the preparation of mesoporous bioactive glasses (MBGs) andinvestigation of their properties as drug delivery system and gene transfection carrier. Themain contents and conclusions are as follows:(1) Ordered MBGs were synthesized by sol-gel co-precipitation method and the effects of theacidic pH value and the kind of template on the ordered mesoporous structure as well asthe in vitro bioactivity of MBGs were investigated. The results showed that the orderedMBGs with2-dimensional (2-D) hexagonal structure can be successfully synthesizedusing P123as structure-directing agent under the pH value of0.5,1and1.5, and thedegree of ordered pore increased with the decrease of pH value. A disorderly porestructure was obtained when used F08as template. The in vitro bioactivity test showedthat the as-synthesized ordered MBGs had an ability of inducing apatite formation.(2) Acid and acid-alkali catalyzed mesoporous bioactive glass microspheres weresuccessfully synthesized via combination of sol-gel and water-in-oil (W/O)micro-emulsion methods. The loading/release properties of Alendronate sodium (AL) andbovine serum albumin (BSA) on MBGMs were studied. Results showed that both of acidcatalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkalicatalyzed mesoporous bioactive glass microspheres (MBGMs-B) exhibited regularspherical shape but with different internal porous structures, i.e., a dense microstructurefor MBGMs-A and internally porous structure for MBGMs-B. MBGMs with differentchemical compositions were also prepared by acid-alkali co-catalyst method with particlesize in the range of2-10μm. The specific area, average pore size and total pore volume ofMBGMs increased with the CaO content. The in vitro bioactivity tests indicated that theapatite formation rate of MBGMs-B was faster that of MBGMs-A and increased with theCaO content. AL can be absorbed into the pores of MBGMs by the interaction with Ca2+ in the pore wall. The absorption amount increased with the increase of CaO content, theAL release profile exhibited a sustained release pattern. The MBGMs can also be used toload macromolecules such as BSA which is mainly physically absorbed. The absorbedBSA amount was related to the surface areas and chemical composition of MBGMs. Theabsorption amount and release duration can be improved by surface modification of aminogroup on the MBGMs. The cell tests showed that the MBGMs possessed goodbiocompatibility.(3) The effects of alkaline pH values and alkaline catalysts on the morphologies andmicrostructure of MBGMs were studied. The results showed that the agglomeratedbioactive glasses nanoparticles can be obtained using buffer solution with a pH value of7-8as catalysts. Regularly spherical MBGMs can be prepared under the catalysis oftriethanolamine, diethanol amine and ammonia water. Triethanolamine-catalyzedMBGMs exhibited a more uniform spherical morphology and good dispersity. All thesamples showed the ability of inducing HA formation after soaking in simulated bodyfluid (SBF).(4) Radially fibrous mesoporous bioactive glass microspheres (rMBGMs) were successfullysynthesized using continuous microemulsion method. The microsphere size, fibrouslength and space can be easily tuned by changing the kind of templates. The rMBGMssynthesized by cteryl pyridine bromide (CPB) showed larger fibrous length and space andsmaller particle size than rMBGMs obtained by cetyl teimethyl ammonium bromide(CTAB). The particle size distribution was broaded by increasing the addition amount ofCaO. The rMBGMs can be used to delivery anti-cancer drug-doxorubicin hydrochloride(DOX), the DOX released from DOX-loaded rMBGMs was in a sustained pattern and theDOX-loaded rMBGMs can entered into cell and exhibited significant inhibition effect.After amine modification, the rMBGMs-NH2can be used as a gene carrier for genetransfection and the optimum transfection conditions in Human kidney epithelial cells(293T) was5μg DNA with a50:1mass ratio of rMGBMs-NH2/DNA.(5) Luminescent europium-containing mesoporous bioactive glasses were synthesized using sol-gel technique by adding Eu2O3in glass network. The results showed that theluminescent intensity increase with the increase of Eu2O3and still exhibited a certainluminescent intensity even after soaking in liquid environment. The addition of Eu2O3increased the average pore size and total pore volume and had no influence on in vitroapatite-forming ability. The cytotoxicity assay showed that the cell viability was sensitiveto ionic concentration of Eu-containing mesoporous bioactive glasses extracts.