Preparation And Characterization Of Cellulose-based Polymeric Hollow Microspheres And Magnetic Hybrid Microspheres

In the past few decades, polymeric hollow microspheres as a novel type of polymericmaterials have attracted considerable interests in the development of drug delivery system,mainly owning to their favorable surface effect, volume effect and biocompatibility. In thisthesis, I have chosen a natural polymer, hydroxypropylcellulose （HPC）, as a biocompatible andbiodegradable template to prepare two kinds of polymeric hollow microspheres using differentpolymerization methods: hollow microgels and hollow hydrogel capsules. Then I haveinvestigated drug loading capacity and releasing behaviors of these polymeric hollowmicrospheres as drug carriers. In addition, I have also fabricated magnetic hybrid microspheresthat were based on the cellulose polymers, and explored their potential application as a newmagnetic-targeted drug carrier for drug delivery. The major results obtained in this dissertationare described as follows:1. I have developed a convenient approach for the preparation of microsize hydrogelscomposed of crosslinked poly（acrylic acid）（PAA） and poly（N-isopropylacrylamide）（PNIPAm）.First, semi-interpenetration polymer networks of hydropropylcellulose （HPC） andPNIPAm-co-PAA copolymer were formed through copolymerization and crosslinking ofmonomer acrylic acid and N-isopropylacrylamide in HPC aqueous solution. After selectiveremoval of HPC from networks by ionization of PAA units and disruption of hydrogen bondingwith the increase of pH, PNIPAm-co-PAA microgels were obtained, whose volume wasconfirmed to be responsive to both temperature and pH. Doxorubicin hydrochloride （Dox）could be encapsulated in PNIPAm-co-PAA microgels with high drug loading driven by theelectrostatic interaction. A characteristic sustained-release of Dox from the microgels wasobserved under physiological pH and temperature. In in vitro cell experiments, the drug-loadedmicrogels could be taken up by LoVo cells and release their payload in cell cytoplasm withoutloss of drug efficacy. This indicates that PNIPAm-co-PAA microgels might be a potential drugdelivery carrier especially for water-soluble or polypeptide drugs. 2. I have demonstrated a convenient approach for the preparation of PNIPAm-PAAhydrogel capsules, which were fabricated by a templated method in aqueous solution.Hydrophilic antitumor drug Dox was successfully entrapped in these hydrogel capsules basedon a charge-controlled permeability mechanism, leading to a new high loading capacity of²80%to the weight of the carriers. More encouragingly, the release of drug from thePNIPAm-PAA hydrogel capsules exhibited a slow-rate but sustainable feature, and behaved thedual-responsivity to temperature and pH. In vitro cytotoxicity assay indicated that theDox-loaded PNIPAm-PAA hydrogel capsules have high antitumor activity. Considering thesimple and mild preparation procedure, high drug loading capacity as well as the desireddual-responsive controlled release property, the PNIPAm-PAA hydrogel capsules may serve asa promising candidate for intelligent drug delivery system.3. I have proposed a convenient approach for the preparation of magnetic PNIPAm-PAAhybrid microspheres. In the first step, hollow PNIPAm-PAA nanocapules were synthesized byprecipitation polymerization with HPC-PAA particles as the template. In the second step, theelectrostatic interaction self-assembly method and the in situ reduction method were adopted togenerate the magnetic Fe₃O₄nanoparticles inside the microcpsules. Thus the magneticFe₃O₄/PNIPAm-PAA hybrid microspheres were finally obtained. In addition, a high drugloading capacity and a sustained-release behavior were presented by using the antitumor drugDox as a hydrophilic model drug, indicating that the Fe₃O₄/PNIPAm-PAA hybrid nanospheresmight be used as a new magnetic-targeted drug carrier for the drug delivery system.