Drug Delivery Research Of Polymer And Silica Nanoparticles

Nanotechnology has caused more and more attentions as its potential versality applications in many research fields recently, especially in the drug carriers and drug delivery science. In the present dissertation, the study focused on the application of sillica nanoparticles in nanocarrier drugs and polymeric lipid nanopaticles in fluorescence marker carrier. The dissertation work included two prats:Part I:Preparation and characterization of vincristine sulfate loaded sillica nanoparticles(VCR-SiNPs) via the modified W/O microemulsion method.Due to the nanoparticles drug carrier could overcome the difficulty of anticancer drug's administration efficiency, which can prolong the drug curculation time in vivo, improve the curative effect and reduce the side effect. The silica nanopraticles were developed to encapsulate VCR as drug carriers. Mainly studied the synthesis process and the cell toxity of VCR-SiNPs. The main achievements obtained in this study include:①The water/oil microemulsion method were used to synthesize VCR-SiNPs, and the catalyzers were HCl and HF. The preparation nanoparticles have a spherical appearance and have a mean diameter of 100nm. To optimizing the nanoparticles formulation, the influence of HCl:NaF molar ratio and amount of VCR were investigated. We found that the NPs size increased with the catalyzer molar ratio increasing. When VCR:TEOS molar ratio in the formulation reached 5:1, the VCR entrapment efficiency reached 72.6±0.7% and the drug loading efficiency reached 7.26±0.16%.②The investigation on the drug release via dialysis method, and the drug release pattern consisted of two phases, with initial exponential phase followed by a slow phase, which revealed that VCR-SiNPs could make the drug release steadily and slowly.③MTT assay method was utilized to evaluate cytotoxicity to tumor cells (MDA-MB-231) of different medications of VCR-SiNPs and VCR. Meanwhile, the SiNPs were also investigated. The result showed that the IC50 value of VCR-SiNPs was 5.4μM. The effectiveness of VCR-SiNPs against the MDA-MB-231 cells was significantly enhanced compared with free VCR.④Studied the stability of VCR-SiNPs under light, high temperature and long term conditions. The results demonstrated that the VCR-SiNPs were more steady than free VCR. PartⅡ:Studies on the preparation and applications of polymeric lipid nanoparticles. We choose indocyanine green (ICG) as fluorescence materials, cisplatin prodrug as model drug, poly (D, L-lactide-co-glycolide) (PLGA) and soybean lecithin as carrier material. In order to develop a nanocarrier system which possess detection and treatment functions. These novel and biodegradable NPs may prove advantageous in tumor detection and drug tracing applications.①Preparation and characterization of ICG loaded polymeric lipid nanoparticles(ICG-PLGA-lipid NPs).ICG was limited by its disadvantageous properties in application, such as poor aqueous stability in vitro, concentration-dependent aggregation and rapid elimination from the body. Encapsulation ICG in the NPs can overcome these limitations. The NPs had an average diameter of 113.4±2.3nm and showed high aqueous stability (over 4 weeks) compared with free aqueous ICG. Ultrafiltration and dialysis efficiently removed unencapsulated ICG from NPs suspension without altering the physical properties of ICG-PLGA-lipid NPs. Importantly, encapsulated ICG demonstrated significant stability against photobleaching relative to free ICG.In vivo imaging test showed that ICG-PLGA-lipid NPs prolonged the circulation time, the fluorescence signals remained detectable at 24h after injection, while there was no fluorescence signals from the free ICG.Fluorescence intensity image as a function of depth in porcine muscle tissue. The detectable penetration depths of ICG-PLGA-lipid NPs were 2.5cm, which indicated that ICG-PLGA-lipid NPs can be used in NIR imaging application.②Research on the preparation and characterization of cisplatin prodrug and ICG loaded polymeric lipid nanoparticles (ICG-Pt-PLGA-lipid NPs).On the basis of polymeric lipid as carrier material, we prepared the NPs loaded with ICG and cisplatin prodrug, studyied the impact of drug adding weight to the entrapment efficiency, evaluated the cell toxcity. We found that these NPs have detection and treatment functions, furthermore, the prepared ICG-Pt-PLGA-lipid NPs can make the drug release slowly, and significantly enhanced the anticumor effectiveness.