Preparation And Study Of Novel Drug-Loaded Microcapsules

Gene drug is the new drug to be candidated of utilizing gene sequence data, analyzing the information, with high-throughput gene expression, high-throughput functional screening, and researching the efficacy of in vitro and in vivo. Gene drugs can be used not only to treat diseases, but also to prevent diseases. Gene therapy is the treatment of diseases by delivery of normal genes or therapeutic genes into specific cells of patients to correct or supplement defective genes responsible for disease development. Now, the vectors are divided into two kinds, including viral and non-viral vectors. Although with highly efficient of gene expression, there are many defects of the viral vectors, such as the security of replication competitive and industrialization. The advantages of non-viral gene vectors are as follows: relatively safer, easier to manufacture, less restricted to the size of the vectors and the style of the nucleic acid,can carry Oligonucleotide of 20bp and Plasmid DNA of 1000Kbp or even langer; low immunogenicity and toxicity, easily to combine with other substances,and the most important one is the target specific. The non-viral vectors are divided into two styles: liposomes and polymer carriers. The polyehtylenimine(PEI) is a kind of polymer commonly used in the paper manufacture, formed with the polymerization of aziridine monomers with the catalysis of acids. In the structure there are so many cations of PEI that can strongly combine with DNA and cells, also can pack plasmid DNA to nano- polyplexes.The protein of this thesis belongs to the Polypeptide and protein, is a kind of biological macromolecules. Because of the short half-life, susceptible degradation of enzyme, difficultily transiting from the film, protein drugs are limited to use in clinical.It will provide new opportunities to protein drugs that wrap it into biodegradable polymer material. But the structure of the protein is so complex that can lose effectiveness and possibly induce adverse reactions, so how to maintain the integrity of the structure is the most important question of the protein drugs.To transit the gene drug and protein drug into bodies without activity influenced, we prepare drug-loaded mircocapsules by using the templates and self-assembled of layer-by-layer technology.Because of the protein molecules can be strongly adsorbed to the nano-inorganic particles in solution, the particles can be used for removal exotoxin, endotoxin, immune complexes of pathogen, products of degradated by necrotic tissue, and other harmful substances, also as the foundation of microbiological and compound drugs.In the first part, we get the nano-silica to be amino-modified, than adsorpted drug molecules. We use it as the template and repeatedly adsorpt polyethylenimine/ polyacrylic acid(PEI/PAA), that is, we prepare polyelectrolyte particles with drug-loaded silica. Finally, we can get the drug-loaded mircocapsules by dissoloving the silica using hydrofluoric acid. Though the pictures of the Transmission Electron Microscopy (TEM), we can note that the capsules are spherical and hollow obviously, the size is uniform, dispersion is very well. The experiments proved that the self-assembled of layer- by-layer technology is a good method to prepare drug-loaded encapsules with high drug-adsorpting rate and drug-containing rate, and without impacting the drug activity. At the end of this part, we discuss the effection of the size of the silica particles that the drug loading will decrease when increase the size.In the second part, we get drug-loaded particles by co-precipitation technology and prepare encapsules. Firstly, we make the drugs in along the formation of calcium carbonate particles from the calcium chloride and sodium carbonate by co-precipitation technology. Secondly, we use it as the template and repeatedly adsorpt polyethylenimine/polyacrylic acid(PEI/PAA) by using the LbL technology, that is, we prepare polyelectrolyte particles with drug in calcium carbonate particles. Finally, we get the drug-loaded mircocapsules by dissoloving the calcium carbonate particles using EDTA. Though the pictures of the TEM, we can see that the capsules are obviously hollow sphere, which the size is uniform and the dispersion is well. The experiments proved that it is a good method to prepare drug-loaded encapsules with high drug-containing rate, and without impacting the drug activity. At the end of this part, we discuss the effection of the stirring speed during the formation of calcium carbonate particles, and get a conclusion that size of the particles will increase when decrease the stirring speed, and unconspicuous effect to the drug-containing rate.It is a new method to prepare microcapsules by using self-assembled of Layer-by-Layer technology. We can control the size and shape of the capsules by adjusting the diameter and shape of the templates, and control the speed of drug releasing by different layer number of absorption;in addition, we can choose different polyelectrolyte materials to adjust to a variety of necessary. These special performance microcapsules are worth to applying to biochemical, pharmaceutical, drug controlled release, catalytic, and other areas.