Study On Preparation And Characterization Of Core/Shell Paclitaxel-Loaded P(LLA-CL) Nanofibers As Drug Delivery System

Electrospinning is a process that produces polymer fibers under the action of an external electric field imposed on a polymer solution or melt. Electrospinning technology is a simple and cost-effective method to prepare ultrafine fibers.In the past decades,significant progresses were achieved on theoretical and experimental studies.The diameter of electrospun fibers is usually 1-3 orders smaller than that of common fibers prepared by conventional spinning techniques.With larger specific surface area and higher porosity compared to commercial textiles,electrospun fibers are excellent candidates for filters,nanocomposites,wound dressings and so on.In biomedical fields,ultrafine fibers prepared by elelctrospinning have been widely used in tissue engineering scaffolds, drug delivery and controlled release,which has attracted more and more attention in the world.Paclitaxel(PTX),one of the best antineoplastic drugs in the past decades,has been used to heal many cancers,especially for breast cancer and ovarian cancer.Like many other anticancer drugs,PTX has many difficulties in its clinical administration due to its poor water-solubility. Therefore,a surfactant called Cremophor EL had been employed,but it has been found to cause serious side-effects,such as hypersensitiveness and shock.In order to solve the problem of low water-solubility,harmful side-effects and enhance the bioavailability of the paclitaxel,coaxial electrospun polymeric fibers as drug delivery system were investigated in this dissertation.The preparation and characterization of fibers,drug release,release model,degradation,biocompatibility and anti-tumor activity of PTX-loaded P(LLA-CL) ultrafine fibers were studied in vitro. The research was mainly concerned with the following aspects.1.Preparation and Characterization of Paclitaxel(PTX)-Loaded P(LLA-CL) fibersPTX-loaded P(LLA-CL) fibers,PTX as the core and P(LLA-CL) as the shell,were prepared via the coaxial electrospinning.The characterization of scanning electron microscopy(SEM),transmission electron microscopy(TEM),X-ray diffraction,infrared spectroscopy, tensile testing,contact angle,water absorption and porosity of core-shell PTX-loaded P(LLA-CL) fibers were investigated.The results showed that there were no reaction between paclitaxel and p(LLA-CL) and both of them maintained the basic chemical properties via coaxial electrospinning. The critical concentration of preparing the P(LLA-CL) core-shell structure fiber was proved to be 2%.With excellent mechanical properties and controllable porosity,P(LLA-CL) has shown potential application prospect as biomaterials for tissue engineering scaffold,drug release and so on.2.Drug release and the release model of PTX-loaded P(LLA-CL) fibers in vitroHigh performance liquid chromatography(HPLC) method was developed for vitro assay of paclitaxel content,release as well as in situ absorption in P(LLA-CL) fibers.The effect of the inner feed rate on diameter the size of the distribution,entrapment efficiency and drug loading were investigated.Meanwhile,drug release and the release model of drug-loaded fibers were investigated in vitro.The results showed that the actual value of drug loading of PTX-loaded P(LLA-CL) fibers was close to the theoretical value,and the encapsulation efficiency of drug-loaded fiber reached 87%.The release rate of paclitaxel from P(LLA-CL) decreases with increasing drug-loaded content.The way of drug-loaded fibers could achieve the primal purpose to prolong the drug's action time and decrease administration times.The investigation of paclitaxel release kinetics from P(LLA-CL) fibers could be described by Wellbull equation as well as Ritger-Peppas equation.3.PTX-loaded P(LLA-CL) fibers in vitro degradation, biocompatibility and in viro anti-tumor activityDegradation and degradation mechanism of PTX-loaded P(LLA-CL) fibers were investigated in vitro.The anti-tumor activity and biocompatibility of the PTX-loaded P(LLA-CL) fibers and blank P(LLA-CL) fibers were evaluated using MTT method and HE stained method in vitro.The results showed that the degradation behavior of PTX-loaded P(LLA-CL) was not obviously observed within 6 months, which is suitable for long-term release of the drug carrier.The results of MTT method and HE method showed that paclitaxel of fibers has effectively inhibit activity for proliferation of Hela cells.The PTX-loaded fibers could not only maintain the bioactivity of paclitaxel but also enhance its bioavailability,which exhibited time and content dependence.