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Studies of Fa-Targeted Mesoporous Silica Nanoparticles and Drug-Loaded Plga Films in Drug Controlled Release

Author: PangJianMei
Tutor: ZuoYuXia
School: Shandong University
Course: Pharmacy
Keywords: mesoporous silica nanoparticles (MSNs) ionic liquids SBA-15 PLGAfilm
CLC: R94
Type: Master's thesis
Year: 2012
Downloads: 304
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Abstract

Mesoporous silica nanoparticles (MSNs) are solid materials, which are comprised of a honeycomb-like porous structure with hundreds of empty channels (mesopores) that are able to absorb or encapsulate relatively large amounts of bioactive molecules. MSNs have several attractive features as follows:(1) High surface area (>900m2/g) and large pore volume(>0.9cm3/g), which allows it to absorb or encapsulate large mounts of drug molecules;(2) Stable and ordered pore framework, which allows to better control over drug loading and release;(3) The uniform and tunable pore size (2-10nm) allows it to adjust the loading of different drug molecules and to study the kinetics of drug release with high precision;(4) There are silanol groups on both of the internal surface and external surface, which makes it simple to be modified;(5) Silica materials are non-toxic and biocompatibility, which is crucial for many biomedical applications. These unique features make MSNs excellent candidates for controlled or targeted drug delivery systems. So the synthesis and modification of MSNs have received much attention recently.Room-temperature ionic liquids (ILs) are attractive environmentally benign solvents for organic chemical reactions, separations, and electrochemical applications. In recent years, the advantages of ILs in inorganic nanomaterials synthetic processes have received more and more attention due to their unique physical and chemical properties. In this study, we prepare hollow or porous silica particles by a simple acid gelation route in IL1-butyl-3-methylimidazolium tetrafluoroborate (BmimBF4) using the sodium silicate as the reactant. Furthermore, the drug release behavior of the synthesized porous silica is studied to reveal their potential use in drug delivery system. Doxorubicin hydrochloride (DOX), a potent antibiotic, is the first line treatment used for a wide range of cancers. However, due to the lack of ability to target cancer cells, it presents major drawbacks such as drug resistance and nonselective cytotoxicity leading to severe side effects. In order to improve therapeutic efficacy of DOX, increase local DOX concentration and reduce systemic side effect, various drug delivery systems have been reported, such as liposomes, polymeric nanoparticles, and polymer conjugates. Folic acid (FA), one of the well known receptor mediated targeting moieties, shows high binding affinity to tumor cells using the specific ligand targeting model. In this experiment, we prepare amino-functionalized SBA-15by ring-opening polymerization of aziridine, then highly branched poly(ethylene imine)(PEI) is grafted on to the surface. Therefore, folic acid can be covalently conjugated to PEI/SBA-15by amide reactions to achieve selective targeting to tumors. SEM, Nitrogen physisorption measurements, FTIR, Zeta potential and TG are used to detect the particle morphology, particle size, surface area, mesopore size, surface potential and modification content. DOX is loaded into MSN by immersion and the drug loading content is determined by TG. The drug loading content in SBA-15and FA/PEI/SBA-15is7.4%and4.3%, respectively. The in vitro release studies are carried out in dialysis bags in mimic release fluid. The results reveal that the drug-loaded MSN exhibits the typical sustained release behavior. MTT assays evaluate the particle-induced cytotoxic effects and cell inhibition rates. Fluorescence microscope and flow cytometry are employed to quantify the cell uptake and targeting. The results show that FA/PEI/SBA-15can decrease the cell cytotoxicity after FA is conjugated on PEI/SBA-15. The DOX-loaded mesoporous nanoparticles exhibit greater cytotoxicity than free DOX. DOX-FA/PEI/SBA can target to FA-receptor-positive HeLa cells, but not to FA-receptor-negative A549cells.Besides, we study drug-loaded PLGA films. Nowadays, poly(lactic-co-glycolic acid)(PLGA) is widely applied in controlled drug delivery systems due to its biodegradability, toxicological safety, and good biocompatibility. As a drug carrier, PLGA has the potential to control drug release from a few days up to several months. In this study, we present a very simple and general route to prepare ibuprofen-loaded films. The drug loading content can be well controlled by changing the weight ratio of ibuprofen (IBU) and PLGA. The drug loading percentage for the samples of WIBU/WPLGA=1/5,1/3and1/2are14.7±0.2%,22.0±1.6%and29.7±0.4%, respectively. SEM, XRD and DSC were used to detect the film morphology and the physical chemistry properties. The in vitro release studies are carried out in dialysis bags in mimic release fluid. The results reveal that the drug-loaded films exhibit the typical sustained release behavior and the release rates of IBU from these films can be well controlled depending on the drug loading content and the pH of the release mediums. The results reveal that the simple and basic method can syntheis IBU/PLGA films with typical sustained release behavior and the as-prepared products show their potential applications in drug controlled delivery system.

Studies of Fa-Targeted Mesoporous Silica Nanoparticles and Drug-Loaded Plga Films in Drug Controlled Release

Abstract

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