The utility of mesoporous silica nanoparticles (MSNs) has been repeatedly proven in a wide range of biomedical applications. The general morphology of these particles is easily modifiable by various post-grafting possibilities and adjustments within the surfactant-based template. The synthesis of multilamellar vesicular silica nanoparticles has led to the discovery of beneficial attributes regarding said particles. Depending on the synthesis process, various parameters are affected including packaging capacity, stability, drug adsorption and release. This research focused on synthesis and characterization of multilamellar MSNs using a cationic-cationic co-surfactant templating route testing various ratios of cetyltrimethylammonium bromide (CTAB) and didodecyldimethylammonium bromide (DDAB). TEM imaging showed clear differences in size and morphology between the different samples, and was further characterized by BET and BJH analysis. All multilamellar nanoparticles did exhibit a similar pore size distribution and overall gradual release of drug contents. However, the degree of drug adsorption and overtime drug release was clearly influenced by the number of layers of the MSNs, proving the utility of adjusting the template. Further experiments could be conducted to validate the utility of beta- cyclodextrin as a template regulator and to investigate both biocompatibility and biodegradability of the multilamellar MSNs.
Nanomaterials are increasingly valued tools in drug delivery research as they offer enhanced stability, controlled release and more effective drug encapsulation. Though yet to be introduced in clinical trial, mesoporous silica nanoparticles are promising delivery systems, due to their high chemical and mechanical stability while remaining biodegradable. This work provides proof of concept for particle based vaccines as cost-effective alternatives for dendritic cell immunotherapy. Synthesis and surface chemistry of the nanoparticles are optimized for protein conjugation and nanoparticles are characterized for their physicochemical properties and biodegradation. Ovalbumin is used as a model protein to load nanoparticles to produce a nanovaccine. The vaccine is tested in vitro on dendritic cultures to verify particle and vaccine uptake, toxicity, maturation effects and explicitly ovalbumin cross-presentation on MHC class I molecules. The optimized synthesis protocol renders reproducible mesoporous silica nanoparticles, resistant against agglomeration, within the required size range and have carboxylic surface functionalization necessary for protein conjugation. They are biodegradable over a time span of 1 week. This period is adjustable by changing synthesis parameters. UV sterilization of the particles does not induce quality loss, nor does it have toxic effects on cells. Treatment with mesoporous silica nanoparticles increases expression of MHC and costimulatory molecules of dendritic cells, indicating an adjuvant effect of nanoparticles on the adaptive immune system. Nanovaccine uptake and cross-presentation of ovalbumin are observed and the latter is increased when delivered by nanoparticles as compared to control conditions. This confirms the large potential of mesoporous silica nanoparticle based vaccines to replace dendritic-based active specific immunotherapy, offering a more standardized production process and higher efficacy.
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