Electrospun Plga/Gelatin Composite Nanofibers For Controllable Release Of Multiple Hydrophilic And Hydrophobic Drugs

The electrospun nanofibers have showed various advantages such as largesurface area, hight porosity and a complex porous structure, which have been widelyused in tissue engineering scaffolds and drug delivery. And the nanofibers can beserved as locally controlled release systems, but most of nanofibers have focused onthe sustained release of a single drug, which often can not satisfy the requirements inclinical therapies. Therefore, novel nanofibers for controllable release of multipledrugs shoud been prepared, and therapeutic efficacy can be maximized if multipleanticancer drugs with distinct characteristics and action mechanisms can be deliveredto the same cell and release in individual behaviors. And the nanofibers can deliveranticancer drugs to kill the tumor cells and endow a favorable microenvironment fortissue construction of tumor defects, thus contributing a long-term tumor healing.Thus the nanofibers will play an important role in cancer therapy.As the locally controlled release fibers, they can not only control multiplehydrophobic and hydrophilic drugs stustained release in individual properties, butalso have favorable biocompatibility and mechanical strength. In the paper, toimprove the hydrophily and biocompatibility of fibers, and gelatin (GE) was blendwith poly(lactide-co-glycolide)(PLGA) to form the stable PLGA/GE nanofibers byelectrospinning technology. Firstly, novel PLGA/GE nanofibers were successfullyfabricated by emulsion electrospinning. Then, the PLGA/GE fibers encapsulated withDOX@mZnO were successfully fabricated. These composite fibers could encapsulateboth hydrophilic and hydrophobic drugs releasing in individual release properties.And the physicochemical properties, drug entrapment, in vitro drug release and invitro cell vibility of composite nanofiber were investigated. The following workswere done in the thesis:(1) Novel biocompatible PLGA/GE nanofibers with favorable biocompatibilityand mechanical strength were prepared, which could serve as an innovative type oftissue engineering scaffold or ideal controllable drug delivery system. Bothhydrophobic and hydrophilic drugs, Cefradine and5-Fluorouracil (5-FU) were successfully loaded into PLGA/GE nanofibers by emulsion electrospinning. Toimprove the surface properties of the materials for cell adhesion, the natural bioactiveprotein GE was incorporated into the nanofibers. Nanofibers were characterized byscanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanningcalorimetry (DSC), contact angle and tensile measurements. Emulsion electrospunfibers with GE had perfect hydrophilic and good mechanical property. The in vitrorelease test showed that the Cefradine in emulsion electrospun fibers achieved lowerburst release, while5-FU showed a fast release manner. The cells cytotoxicityexperiment indicated that emulsion electrospun PLGA/GE composite fibers were lesstoxicity and tended to promote fibroblasts cells attachment and proliferation. Allresultes implied that the PLGA/GE composite fibers had promising potentialapplication in tissue engineering or drug delivery.(2) A novel mZnO/PLGA/GE electrospun composite fibers encapsulated withboth hydrophilic drug (doxorubicin hydrochloride, DOX) and hydrophobic drug(camptothecin, CPT) were fabricated. mZnO was firstly used to encapsulate DOX.Then, the DOX-loaded mZnO (DOX@mZnO) and CPT were mixed with PLGA/GEsolution to fabricate electrospun hybrid nanofibers. The in vitro release resultsdemonstrated that the CPT in the composite fibers presented a fast release manner,while DOX showed a sustained release behavior. The cell cytotoxicity test indicatedthat the composite nanofiber with two drugs showed strong antitumor efficacy againstHepG-2cells. Moreover, the addition of GE increased the hydrophilicity ofcomposite fibers. More importantly, the incorporated of mZnO within PLGA/GEnanofibers can not only significantly reduce the burst release of DOX, but alsoimprove the mechanical durability of the composite nanofibers. Thus, the compositenanofibers could be a versatile drug delivery system encapsulated with bothhydrophilic and hydrophobic anticancer drugs as implantable scaffolds for potentialpostsurgical cancer treatment.