Preparation, Characterization And Controlled Release Of Mosoporous Silica Nanoparticles As Drug Carriers

The use of nanotechnology in drug delivery is a rapidly expanding field. Biodegradable or nontoxic nanomaterials have the most promising application potentials in nanomedicine. Recent research has focused on developing structurally stable drug delivery systems that are able to deliver a relatively large amount of drug molecules without any premature release problem to targeted tissues or even intracellular organelles. Among many structurally stable materials that have been investigated for drug delivery, silica materials with defined structures and surface properties are known to be biocompatible. Silica is often the material of choice to enable the biological use of inorganic nanoparticles. Mesoporous silicas are comprised of a honeycomb-like porous structure with hundreds of empty channels (mesopores) that are able to absorb/encapsulate relatively large amounts of bioactive molecules. The unique properties, such as high surface area large pore volume, tunable pore size with a narrow distribution, and good chemical and thermal stability, of these materials make them potentially suitable for various controlled release applications.Biodegradable polymeric nanoparticles typically consist of polylactic acid (PLA), polyglycolic acid (PGA), poly(D,L-lactide-co-glycolide) (PLGA), and polymethyl methacrylate (PMMA). Polymeric materials exhibit several desirable properties including biocompatibility, biodegradability, surface modification, and ease of functionalization of polymers. Polymeric systems allow for a greater control of pharmacokinetic behaviour of the loaded drug, leading to more appropriate steady levels of drugs. These attributes make it a candidate system for effective entrapment or encapsulation of biotech drugs that are usually sensitive to the changes in the surroundings such as proteins, genes or DNA.Based on the research of mesopores silica nanoparticles and PLGA nanocapsules as drug delivery system, the research interest of this thesis focused in exploiting a novel nanoscale drug delivery system which had the double advantages of the silica and PLGA and used for anti-cancer drugs delivery. The results of each part are listed as follows: 1. Core-shell nanoparticles of Au@SiO2 with a diameter of approximate 45–60 nm and wall thickness in range of 3–10 nm were synthesized by using 40 and 50 nm gold nanoparticles as the templates. The mesoporous particles are regulated by 3-aminopropyltrimethoxysilane addition. Hollow mesoporous silica nanocapsules (HMSNs) were prepared by using sodium cyanide to dissolve the gold cores. The characterization of Au@SiO2 and HMSNs by transmission electronic microscope indicated that the silica shells were uniform and smooth, and also the porosity was proved by ?uorescein isothiocyanate (FITC) release experiments. The ratio of hollow core to HMSNs is more than 70%. HMSNs were subsequently used as drug carrier to investigate FITC (as a model drug) release behaviors in vitro. Fluorescent spectrometry was performed to determine the release kinetics from the HMSNs. The release profiles are significantly different as compared with the control (free FITC), which show that HMSNs are good drug carriers to control drug release, and have high potential in therapeutic drugs delivery in future applications.2. Light-sensitive core-shell nanoparticles of Au@SiO2 with a diameter of approximately 45 nm and a silica shell thickness of within 5 nm were prepared using 40nm diameter gold nanoparticles as templates. The light-sensitive molecules of vitamin C (Vc), 5(6)-carboxy?uorescein- N-hydroxysuccinimide ester (FLUOS), polyvinyl alcohol (PVA), and 2,5-dihydroxy -p-benzoquinone(DHBQ) were fabricated and embedded in silica shells. The mesoporous silica shells were controlled by regulating 3-aminopropyltrimethoxysilane (APS) addition because APS molecules can bind to gold nanoparticle surfaces at different percentages. Silica nanocapsules were prepared using sodium cyanide to dissolve gold cores. The morphology of Au@SiO2 and silica nanocapsules was characterized by transmission electron microscopy (TEM). The dissolution time courses of prepared nanoparticles were investigated after irradiation with a super high-pressure mercury lamp (500 W). It was found that the silica shells became more condense and pore sizes shrunk after light sensitive molecules decomposed following light irradiation because the light-irradiated nanoparticles dissolved more slowly than the non-light-irradiated nanoparticles. From the TEM micrographs of silica nanocapsules, silica nanocapsule shrinking was also observed under high-density electron current. By our method, with a diameter of approximately 45 nm light-sensitive silica nanocapsules were obtained. These light-sensitive nanocapsules have high potential in future applications of the delivery of therapeutic drugs.3. PLGA is a biodegradable and biocompatible polymer material for drug deliver system. The aim of this study is to synthesize drug-loaded PLGA nanoparticles for sustained release and its anticancer effect in vitro. PLGA nanoparticles were prepared with modified solvent evaporation method. PLGA nanoparticles encapsulated fluorescent isothiocyanate (FITC, as a model drug) and paclitaxol (therapeutic drug) were prepared with the diameter of within 800 nm as drug carrier. The release kinesics and anticancer effect for HeLa cells of the PLGA nanoparticles were further investigated. There was a peak of accumulative FITC release from the FITC-loaded PLGA nanoparticles at approximate 18 h. The inhibition rate of HeLa cell growth was studied by 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium (MTT) colorimetric assay assay. Cells were killed by paclitaxol-loaded PLGA nanoparticles. Apoptosis of HeLa cells maybe also occurred due to the sustained release of paclitaxol from the PLGA nanoparticles, which showed that PLGA nanoparticles encapsulated paclitaxol are promising as a controlled drug delivery system in future clinic application.4. A novel core-shell nanoparticle with double shell coatings (silica and PLGA) with the total shell thickness of 8.7±1.3 nm was prepared. The outer shell of PLGA is biodegradable and used for controlled and sustained release, and the inner shell of silica is mesoporous for the preservation of the chemical radiation therapeutic of methyl viologen (MV), an oxidant that produces reactive oxygen species during cancer radiation therapy. The dissolution time course data and transmission electron microscopy images showed that the novel nanoparticles (Au@SiO2&PLGA) have been successfully prepared, and silica and PLGA coated well the gold (Au) template surfaces. Nanocapsules (MV@SiO2&PLGA) were obtained after the gold templates were dissolved using sodium cyanide. The sustained release property was characterized through detecting fluorescence quenching time course of fluorescent isothiocyanate after mixing with MV@SiO2&PLGA nanocapsules that encapsulate MV molecules. The sustained release of MV molecules could be extended to approximately four weeks. This novel delivery system has high potential in future application for the delivery of therapeutic drugs, particularly for the treatment of cancer by radiation therapy.