A Research Of Sustained/Controlled Drug Release Based On Mesoporous Silica

Mesoporous silica nanomaterials are used as the host and the modifiers whichpossess pH sensitive, thermo-sensitive or enzyme responsive characters were employedto control the release for tumor targeting due to its low pH value and special enzyme incolon (e.g. β-mannanase). Combined chemotherapy with the hyperthermia, thecytotoxicity can be enhanced obviously, Cell experiments were carried out to evaluatethe biocompatibility, and the enhanced cytotoxicity was investigated by themulti-therapy technology (e.g. anti-tumor drug or hyperthermia). Various methods wereused to characterize the structure of the system. The method and technology ofsynthesis, assembly, and modification were summarized for the further use. Therelationship among material structure, properties, drug release mechanism andtherapeutic effect were investigated in detail. The anti-cancer properties of the systemwere evaluated. This work can offer many important basic data not only for thesynergistic anti-tumoral effects on cancer, but also for the efficient and safe clinicalapplication of antitumor drugs. The main contents include the following three aspects:(1) A controlled release system with pH-responsive ability has been presented.Mesoporous bioglass (MBG) was used as the drug carrier and a spontaneousmineralization method was adopted to cap the pores of the carrier with hydroxyapatite(HAp) and to restrict the drug release. Due to the degradation of HAp at acidenvironments, the system shows well pH-sensitive drug release ability. The releasekinetics can be easily adjusted by the mineralization time and the ion concentration ofmedia.(2) The nanocarriers with magnetic Fe3O4nanoparticles core and mesoporous silica(mSiO2) shell were synthesized. Considering the magnetic hyperthermia of Fe3O4underalternating magnetic field (AMF), a thermo-sensitive polymer poly [(ethyleneglycol)-co-(L-lactide)](P(EO-co-LLA)) was used as “gatekeeper” coating outsideFe3O4@mSiO2to regulate the release behavior. The drug loading nanocomposites showthe controlled drug release behavior trigged by the hyperthermia of Fe3O4under AMF.Furthermore, the chemotherapy of DOX combined with magnetic hyperthermia can improve the cytotoxicity obviously.(3) Mesoporous silica materials (mSiO2) with100nm in size was used as the host, and Konjacoligosaccharide (KOGC) was employed to seal the nanopores of mSiO2to inhibit the drug release.The KOGC modified mSiO2(mSiO2@KOGC) retains the drug until it reaches the colonicenvironment where bacteria secrete enzymes (β-mannanase) can degrade KOGC and make drugrelease. The amount of KOGC and enzyme can be used to adjust the release performance.