The Assembly And Property Of Calcium Phosphate And Polymer Hybrid Nano Drug Carrier

With the development of nanotechnology, nanomaterials have been widely uesd in the field of nanomedicine for its inherent physical and chemical properties and structure. Nano drug carriers are an indispensable part of nanomedicine. Nano drug carrier can improve the therapeutic effect of the drug and reduce side effects of drugs through efficiently delivering drugs to the diseased tissues and cells. Calcium phosphate(CaP) is the main mineral found in human bone and teeth. Thus, they are considered as a highly biocompatible inorganic biomaterial and suitable candidates for drug carriers. Calcium phosphate nanoparticles can be quickly dissolved under weakly acidic conditions and release the drug with intrinsic advantages of degradability at certain pH values,which avoid the drug releasing during delivery. However, CaP particles grow quickly to form large agglomerates after preparation, which limit their application in vivo.Moreover, large CaP agglomerates tend to disturb intracellular calcium homeostasis and result in cell death. Therefore, it is essential that calcium phosphate nanoparticles were modified to improve its stability. Here, a series of different materials modified calcium phosphate nanoparticles were designed and prepared with excellent stability, which can load genes and chemotherapy drugs.mPEG-PE(polyethylene glycol-L-?-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. The average size of the hybrid nanoparticles was approximately 30-50 nm and the morphology of the nanoparticles was observed by TEM, which showed that the nanoparticles were spherical and had no obvious aggregation. Effective encapsulation of siRNA in the nanoparticles was above 80%.The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease(RNase) degradation. Moreover, the haemolysis percentage of nanoparicles at the highest concentration of 1000 ?g/mL was still low(12%). The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity.In order to improve the stability of calcium phosphate nanoparticles, mPEG-PLA coating calcium phosphate nanoparticles were prepared by employing a reverse microemulsion method. The average size of the hybrid nanoparticles was approximately 100 nm with a negative charge of approximately-8.2 mV. Effective encapsulation of siRNA in the nanoparticles was about 50% and the colloidal stability of nanoparticles was excellent. Compared with free siRNA, the nanoparticle-loaded siRNA could efficiently deliver siRNA to cells and enhance endosomal escape of siRNAvia endocytosis. No significant cytotoxicity was observed for the cells treated with NPs when the final concentration of nanoparticles was 2000 ?g/mL or less. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention(EPR) effect based on the fluorescence intensities of tissue distribution.In order to simplify preparation methods,we attempt to prepare liposome coating calcium phosphate nanoparticles loading with DOX.The traditional chemotherapy is an indispensable method against cancer. However, its therapeutic efficacy is usually limited by multidrug resistance. The nanoparticles-based drug delivery systems can overcome multidrug resistance and delivery drug to cells. Lipidosome coating calcium phosphate nanoparticles were prepared using a double emulsion-solvent evaporation technique. The average size of the hybrid nanoparticles was approximately 100 nm and enhanced colloidal stability of the nanoparticles. The surface charge of nanoparticles could been controlled change from-42 mV to 45 mV. The nanoparticles could load with water soluble DOX and the drug loading content and drug encapsulation efficiency of the nanoparticles were over 8.2% and 90%, respectively. The cumulative release profiles were investigated at predetermined pH value, the nanoparticles could rapidly release the drug at pH 5.0. Moreover, the nanoparticles can enhance cellular uptake of DOX and effectively overcome multidrug resistance in cancer therapy.