| Liposomes are artificially prepared vesicles made of lipid bilayers. Due to its unique structure, liposomes can entrap water soluble drugs in their internal aqueous phase and lipophilic drugs in the lipid bilayer membrane. In addition, liposomes have good biocompatibility, biodegradability and low toxicity, leading to potential applications in drug delivery systems. However, there remain problems with liposomal stability, size, production scale-up, and the use of toxic organic solvents in their preparation. These restrict the application and development of liposomes. For instance, considering the size issue, it’s reported that liposomes smaller than70nm are taken up by liver parenchymal cells, but those larger than300nm accumulate in the spleen. An optimum size range of70-200nm has been identified as giving the highest concentration of liposomes in the blood. Another study demonstrated that the biodistribution of liposomes depends both on the mean particle size and on the size distribution. Therefore, the development of new liposome preparation methods for controlling over their properties is required.In this thesis, we describe a facile and convenient strategy for the preparation of self-assembled liposomes from nanofibers based on the good water-soluble and spinnability of PVP. In this method, amphiphilic nanofibers composed of the hydrophilic polyyinylpyrrolidone K60(PVP) and soybean lecithin were firstly fabricated using an electrospinning process. As a result of the templating of the nanofibers, PC liposomes were spontaneously formed through melecular self-assembly when the fibers were added to water. The influence of PC on nanofiber formation, and a possible mechanism of templated liposome formation were discussed. On the basis of work before, we chose ketoprofen (KPF) as a model drug, incorporated it into PVP-based nanofibers via electrospinning, and subsequently investigated the self-assembly of KPF-loaded liposomes, the drug entrapment efficiency and the drug release behavior in vitro. The sustained and controlled drug release from liposome was thus exhibits attractive application in drug delivery.This thesis includes the following contents:Amphiphilic PVP-PC composite nanofibers were fabricated using an electrospinning process. As a result of the templating of the nanofibers, PC liposomes were spontaneously formed through melecular self-assembly when the fibers were added to water. Through the characterization of nanofibers and liposomes, we discussed the influnce of PC content on the properties of spinning solutions, composit nanofibers and liposomes. The results of scanning electron microscopy (SEM) showed that pure PVP nanofibers from a10%w/v chloroform and DMAc mixed solution have an everage diameter of1208±71nm. As the PC content of the fibers was increased (from9.1%to33.3%w/w), the nanofiber diamter decreased to572±95nm. However, a further increase in PC content to50%w/w led to a sharp increase in diameter (to1844±63nm). In addition, the results from X-ray diffraction (XRD), differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FTIR) demonstrate that there are electrostatic and hydrophobic interactions between PVP and PC, and these secondary interactions plays a fundamental role in promoting the structural homogeneity of PVP-PC composite nanofibers. The results of dynamic light scattering (DLS) showed that the size of the vesicles produced is closely linked to the PC content in the nanofibers. And increasing the PC concentration results in a lower polydispersity index (PDI) of the self-assembled liposomes, with the lowest index being0.205at a concentration of33.3%. This suggested that, elevating the PC content in the fiber composites is beneficial for the production of vesicles with a narrower size distribution.Using the above spinning conditions, we successfully fabricated PVP-PC-KPF composit nanofibers. With these nanofibers as templates, we preparated KPF-loaded liposomes. The ratio of KPF to phospholipid (PC) on the properties of nanofibers and liposomes has been systematically investigated. Both liposome size and Zeta potential tended to decrease with an increase in the mass ratio of KPF to PC.The dialysis technique was used to remove free KPF from the KPF-loaded liposome suspensions and methanol was used to break up the KPF-loaded 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 the hightest entrapment efficiency (94.6%) was obtained, when the mass ratio of drug to PC up to3:25, and the release of KPF from liposome were closely related to the pH value of the release medium, with the rate of release rising with an increase in pH. The liposomes are observed to release the drug over around24h, suitable for use in a sustained release formulation. |
PDF Full Text Request