Sonochemical Preparation And Property Research Of Multifunctional Drug-loaded Microcapsules

With the fast development of society and the great progress of science and technology, people have been not satisfied with the diagnosis and treatment of some diseases on the macro morphology（tissues or organs, etc.）, and are also gradually extending to the microscopic biology, such as cells, genes, etc. As a kind of novel nano- or micro- carriers, biomolecular microcapsules have drawn much attention in recent years, especially in the biological field and medical field. It is not only because biomolecular microcapsules have good biocompatibility and degradability, and compared with other microcapsules, the walls of biomolecular microcapsules still retain a large number of active groups which can make biomolecular microcapsules endowed with some new features further, such as targeting, thermal responsiveness and p H responsiveness, and so on. In this paper, based on the biomolecular microcapsules prepared by the sonochemical method, a series of multifunctional drug- loaded microcapsules have been designed and prepared, and their synthesis mechanisms have also been expounded. Besides, the morphology and properties of the multifunctional drug-loaded microcapsules have been studied systematically.1. Bovine serum albumin（BSA） microcapsules have been synthesized by the sonochemical method, and some synthetic conditions have also been explored carefully, such as ultrasonic mode, ultrasonic power, ultrasonic time and the concentration of BSA, and finally BSA microcapsules with the small particle size and uniform distribution have been obtained. In addition, the structure and morphology of BSA microcapsules have been studied through doping a fluorescent probe, and it is found that BSA microcapsules are spherical composite particles composed of BSA shells and oil cores. Furthermore, BSA microcapsules have been proved to have a good loading capacity and stability, and they are able to protect inner hydrophobic drugs wel.2. BSA@Fe₃O₄ MNPs with core-shell structure have been synthesized successfully with Fe₃O₄ magnetic nanoparticles（Fe₃O₄ MNPs） as the matrix and BSA molecules as the modifier. Then, by the sonochemical method, BSA@Fe₃O₄ microcapsules（BSA@Fe₃O₄ MCs） with magnetic capsule walls have been prepared further. Through the characterization about the sizes and morphology of BSA@Fe₃O₄ MNPs and BSA@Fe₃O₄ MCs, it has been proved that the preparation of BSA@Fe₃O₄ MCs with magnetic capsule walls are due to the covalent cross- linking formation of BSA@Fe₃O₄ MNPs on the oil- water interface. By the magnetic separation experiments, BSA@Fe₃O₄ MCs have shown an excellent magnetic property. What is more, the encapsulating tests for the fluorescent dye demonstrate that BSA@Fe₃O₄ MCs have a good loading capacity for the hydrophobic drugs.3. Based on the sonochemical method, folic acid（FA） modified magnetic BSA microcapsules（FA-MBMCs） which are a kind of multifunctional drug carriers with targeting and reductive properties have been successfully prepared. FA-MBMCs not only have an appropriate size for the blood circulation and good biocompatibility, but also possess a stable and efficient delivery ability to save the hydrophobic drug for a long time. Besides, as a drug carrier, FA-MBMCs show a good magnetic responsiveness and molecular targeting ability, which makes them move directionally relying on its own magnetism and selectively combine with the targeted tumor cells by the targeting ability of FA. In addition, FA-MBMCs also display an excellent reductive responsiveness, providing a feasible condition for the controlled release of drugs in tumor cel s.4. A novel magnetic and molecular dual-targeting FA-cysteine-Fe₃O₄ microcapsules（FA-Cys-Fe₃O₄ MCs） have been designed and fabricated. The researches show that FA-Cys-Fe₃O₄ MCs have the following characteristics: 1) Fe₃O₄ MNPs and FA molecules are fixed onto the capsule walls of FA-Cys-Fe₃O₄ MCs, so FA-Cys-Fe₃O₄ MCs show a nice magnetic and molecular targeting ability; 2) As a drug delivery system, FA-Cys-Fe₃O₄ MCs present a strong ability to load and save the drugs stably, preventing a leak of the inner drugs; 3) Because the formation of FA-Cys-Fe₃O₄ MCs are mainly dependent on the crosslinking of sulfydryl groups among the Cys molecules, FA-Cys-Fe₃O₄ MCs have a certain reductive responsiveness and can effectively control the release of the inner drugs.5. On the basis of the sonochemical synthesis of BSA @ Fe₃O₄ MCs, we have succeeded in the preparation of a new type of magnetic/molecular dual- targeting and reductive/thermal dual-responsive microcapsules——FA modified BSA@Fe₃O₄ microcapsules（FA-BSA@Fe₃O₄ MCs）. The optical microscope shows that FA-BSA@Fe₃O₄ MCs can be dispersed evenly in water and have a good microstructure. Both SEM and TEM show that the walls of FA-BSA@Fe₃O₄ MCs contain a lot of Fe₃O₄ MNPs. The magnetic separation experiments and hysteresis curves show that FA-BSA@Fe₃O₄ MCs have a good magnetic property. The loading test for coumarin 6 shows that the high doses of hydrophobic drugs can be encapsulated into the microcapsules along with the oil gel. Cellular internalization tests show that FA-BSA@Fe₃O₄ MCs have a molecular targeting ability and can selectively combine with tumor cells, and the tests about the cellular toxicity show that FA-BSA@Fe₃O₄ MCs are non-toxic to the cells. Additionally, the releasing results of FA-BSA@Fe₃O₄ MCs under different conditions show FA-BSA@Fe₃O₄ MCs have a good reductive and thermal dual responsiveness to effectively control the release of the hydrophobic drugs.6. By using the sonochemical method, the novel multifunctional nanocapsules have been successfully designed and synthesized to purposefully load the hydrophilic drugs（HDs）. As a kind of hydrophilic vesicles, HDs loaded multifunctional BSA nanocapsules（HD-Loaded MBNCs） have a good size distribution and morphology. As a kind of carriers, HD- Loaded MBNCs show an excellent magnetism and can move directionally relying on external magnetic field. As a kind of drug systems, HD-Loaded MBNCs present some reductive responsiveness which can realize the controlled release of hydrophilic drugs. Moreover, the experimental results of the cellular internalization show that HD-Loaded MBNCs can be selectively taken in by tumor cells owing to the molecular targeting ability of FA molecules on the capsule wal s.