| Due to electrospun nanofibers’ high surface area, high porosity, small size effectand surface effect, it is widely used as controlled release carrier of anticancer drugsfor postoperative chemotherapy, which has obtained widespread attention. With thedevelopment of electrospinning techniques and the emergence of variousbiodegradable and biocompatible polymer materials, construction of novel drugdelivery system based on electrospun nanofibers remains a scientific challenge in thefield of biomedical applications. Construction of novel nanofiber scaffolds loadedvarious drugs with distinct characteristics and action mechanisms could be used inlocal tumor, to realize drug releasing in a sequential way and maximizing therapeuticefficacy. Construction of novel multifunctional composite scaffolds for antitumor andbioimaging application could be realized real-time tracing and monitoring theinteraction between tumor cells and the tissue engineering scaffolds, as well as thewhole process of postoperative therapy. These have important implications for tumortherapy after surgery.In the paper, novel poly(lactic-co-glycolic acid)(PLGA) composite nanofibersencapsulated with drug-loading micelles was successfully fabricated. It couldencapsulate two hydrophobic drugs at the same time (paclitaxel and brefeldin A) andrealize controlled dual release of two hydrophobic drugs with distinct rates in avehicle. Novel composite nanofibers encapsulated with water-soluble fullerenenanoparticles and antitumor drug (paclitaxel) was fabricated via a simpleelectrospinning method. In vitro cytotoxicity and bioimaging of composite nanofiberswas studied in detail, the results strongly suggested that the electrospun compositenanofibers was able to provide a good alternative for cancer postoperativechemotherapy.The main research contents and results of this thesis are as follows:(1) Chemical bonding and physical embedding polymeric micelles withamphiphilic block copolymer MePEG-PLLA as carrier material were developed ascontrolled release systems for macrolide antibiotic drug brefeldin A (BFA). Chemicalbonding polymeric micelles (MePEG-PLLA/BFA) had average diameter of120nm and4.3%drug-loading efficiency of BFA. Meanwhile, physical embeddingpolymeric micelles (BFA-PM) had average diameter of160nm and4.8%drug-loading efficiency of BFA. All polymeric micelles had spherical and core-shellstructures, regular shape and uniform dispersion. The release profiles of BFA in PBSwere measured by HPLC, demonstrating that the drug had no obvious burst releaseand the controlled release of BFA could be gained for long time. The release profileof BFA in chemical bonding polymeric micelles was a first-order release, slower thanthat of physical embedding polymeric micelles. The in vitro antitumor activity ofpolymeric micelles against human liver carcinoma HepG-2cells was evaluated byMTT method, and the results showed that BFA could be released from the micelleswithout losing cytotoxicity and inhibited HepG-2cells proliferation effectively.(2) PEG-PLLA electrospun nanofibers were developed as a new controlledrelease system for macrolide antibiotic drug brefeldin A (BFA). The average diameterof the BFA-loaded PEG-PLLA fibers was below950nm with smooth surfaces, andthe drug was well incorporated into the fibers in amorphous form. The release profilesof BFA in PBS were measured by HPLC, demonstrating that the fibers had a goodslow-release effect of the drug BFA and the controlled release of BFA could begained for long time. The in vitro antitumor activity against human liver carcinomaHepG-2cells of the fibers contained3wt.%,6wt.%,9wt.%,12wt.%and15wt.%BFA were examined by MTT method, and the results showed that cell growthinhibition rates at72h were64%,77%,80%,81%and85%, respectively.(3) By means of “emulsion-electrospinning”, paclitaxel (PTX) and polymericmicelles containing BFA were successfully loaded into the electrospun PLGAcomposite nanofibers. The emulsion droplets containing drug-loaded polymericmicelles was produced by emulsification of micelles, and then successfullyencapsulated into PLGA fiber. The in vitro release results demonstrated that thelocation of the drugs in the electrospun fibers determined their release profiles. PTX,loaded in the PLGA polymer matrix directly, was released in a relatively rapid rate,while BFA showed a long-term and sustained release behavior due to hindrance fromMePEG-PLLA micelles and PLGA matrix. In vitro cytotoxicity studies revealed thatthe composite nanofibers with two drugs restrained HepG-2cells more efficiently.These results strongly suggested that the electrospun composite nanofibers containing polymeric micelles could realize controlled dual release of two hydrophobic drugs withdistinct rates in a vehicle and were suitable for postoperative chemotherapy of cancers.(4) A novel fluorescent nanofibrous material, consisted of water-solublefullerene nanoparticles and poly(L-lactide)(PLLA) was fabricated via a simpleelectrospinning method. The nanofibers were uniform and their surfaces werereasonably smooth, with the average diameters of fibers ranging from300to600nm.The fullerene nanoparticles were encapsulated within the composite nanofibers,forming a core-shell structure. The nanofiber scaffolds showed excellent hydrophilicsurface due to the addition of water-soluble fullerene nanoparticles. The compositenanofibers used as substrates for bioimaging in vitro were evaluated with human livercarcinoma HepG-2cells, the fullerene nanoparticles’ intense red fluorescence signalalmost displayed in every HepG-2cell nucleus, implying the potential of fluorescentfullerene nanoparticles/PLLA nanofibers to be used as scaffolds for tissueengineering and bioimaging application.(5) Novel PLLA composite nanofibers (PTX/PLLA@C70-TEGs) encapsulatedwith water-soluble fullerene nanoparticles C70-TEGs and paclitaxel (PTX) wassuccessfully fabricated. The nanofibers were uniform and their surfaces werereasonably smooth, with the average diameters of fibers ranging from350to750nm.The nanofiber scaffolds showed excellent hydrophilic surface and good mechanicalproperties. The in vitro release results demonstrated that the release rate of paclitaxelcould be controlled by the content of nanoparticles. With increasing the content ofC70-TEGs nanoparticles, the drug release rate was faster and the total release wasmore. The composite nanofibers used as substrates for cytotoxicity and bioimaging invitro were evaluated with human liver carcinoma HepG-2cells, and the resultsshowed that PTX inhibited HepG-2cells proliferation effectively after controlledrelease from the composite nanofibers. Meanwhile, the fluorescent signal of fullerenenanoparticles C70-TEGs could be detected in HepG-2cell nucleus, which reflected thegrowth state of cells clearly. These results strongly suggested that the potential ofcomposite nanofibers PTX/PLLA@C70-TEGs could be used as scaffolds for tissueengineering, drug delivery and bioimaging application. |
PDF Full Text Request