Self-Assembled Magnetic Liposomes From Electrospun Fibers And Study On Release Evaluation Of Drug Carries

Magnetic nanomaterials have many special characteristics such as high specific surface area, a special magnetic properties, excellent chemical stability and biocompatibility. In recent years, magnetic nanomaterials have attracted great attention from researchers due to their inherent properties. Magnetic nanoparticle drug carrier, which is the product of nanotechnology combined with modern medicine, is a novel drug delivery system with good drug releasing performance that can prolonged duration of the drug action, improve the stability of the drug. So it has been widely applied in the field of medical technology. Nanostructure lipid carriers refers to various molecular assembly synthesis made of lipid. Due to its unique structure, nanostructure lipid carriers can entrap hydrophilic drugs in their internal aqueous phase and hydrophobic drugs in the lipid bilayer membrane. Magnetic liposomes are a kind of suspension of liposome vesicles containing magnetic particles, meanwhile it is also a new type of drug targeting vector and magnetic orientation drug delivery system. This magnetic drug carrier not only includes the potential advantages of magnetic nanomaterials but also can play a potential application of nanostructure lipid carriers. Therefore, to develop a new and facile rout of magnetic liposome preparation methods is particularly required.Electrospun fibers are one-dimensional nanoscale fibers whose secondary structures can be controlled by electrospinning technique. The eletrospun fibers consist of a ploymer filament with functional components dispersed throughout this matrix. In addition, electrospun fibers can act as templates to control the transport and contact of molecular building blocks via secondary interactions, which can result in tightly controlled molecular self-assembly. Fe3O4, a significant member of magnetic nanoparticles, has a function of orientation and positioning as ferromagnetic nuclear in magnetic liposomes.Base on the fruit of those good works, in this thesis, we describe a facile and convenient strategy for the preparation of self-assembled magnetic liposomes from electrospun fibers based on the good hydrophilic and spinnability of PVP K90. In this method, we prepared a novel Fe3O4/PC/PVP composite fibers and then we chose ketoprofen (KPF) as a model drug, incorporated it into the composite fibers via electrospinning with different ratios of drug and phosphatidylcholine. Then drug-loaded magnetic liposomes were prepared by self-assembling from the drug-loaded composite fibers. A possible mechanism for the formation of the drug-loaded magnetic liposomes was proposed. And we investigated the drug entrapment efficiency and the drug release behavior in vitro. The sustained and controlled drug release from magnetic liposome was thus exhibits attractive application in drug delivery. The main research can be summarized as follows:(1) First of all, Fe3O4magnetic nanoparticles were prepared by chemical coprecipitation. In addition, we chose chloroform as a solvent, polyvinylpyrrolidone (PVP K90) as a matrix of fibers formation, Fe3O4magnetic nanoparticles and phosphatidylcholine (PC) as base materials to prepare Fe3O4/PC/PVP composite fibers by electrospinning. The effect of various factors on the morphology of electrospun fibers had been studied systematically. The results indicate that when the flow rate of the solutions was fixed at0.5mL/h-2.0mL/h, the voltage at12kV, the concentration of PVP at6%-8%(w/w), the Fe3O4content at4%-12%(w/w), uniform fibers could be obtained. And it was found that the diameters of the resulting fibers increase as the Fe3O4content, the PVP concentration and the flow rate of the solutions were increased, while decreased with the increase of voltage.(2) Using KPF as a model drug, we successfully fabricated drug-loaded composite fibers, and the ratio of KPF to PC on the properties of fibers has been systematically investigated. The results of scanning electron microscopy (SEM) showed that the diameters of the electrospun fibers decreased with an increase in the mass ratio of KPF to PC. The fourier transform infrared spectroscopy (FTIR) demonstrated that there are electrostatic and hydrophobic interactions between PVP and PC, these secondary interactions plays a fundamental role in promoting the structural homogeneity of the composite fibers and KPF was successfully fixed in the fibers resulting in the drug-loaded fibers.(3) Magnetic liposome has been produced by self-assembly from the drug-loaded fibers through molecular self-assembly technology. We observed the morphology of the magnetic liposomes and self-assembly process by TEM, SPM and the characterization of the magnetic liposomes were characterized by DLS, Zeta potential, and VSM. The results indicate that the average size of magnetic liposomes is200-600nm and moreover, the magnetic liposomes have a good superparamagnetism whose saturated magnetic can be up to59.938emu/g. Meanwhile, with the increase of the ratio of KPF to PC, the size and Zeta potential of magnetic liposomes are become smaller. (4) The dialysis technique was used to remove free KPF from the drug-loaded magnetic liposome suspensions and methanol was used to break up the drug-loaded magnetic liposomes. The entrapment efficiency (E.E.) of KPF was determined by UV spectroscopy at λ=260nm. We also dicsussed the release behavior of KPF as a model drug from liposomes in vitro. The results showed when the mass ratio of drug to PC up to2:5, the hightest entrapment efficiency (84.6%) was obtained. From the curves of drug release, the magneitc liposomes with different ratio of KPF to PC have good release performace, suitable for use in a sustained release formulation.