Semi-interpenetrating Polymer Network Hydrogels And Cationic Polymer Gene Carriers

Hydrogels are insoluble, cross-linked three dimensional network structure composed of hydrophilic polymers, which do not dissolve in water at physiological temperature and pH, but absorb a great deal of water. Hydrogels have increasingly attracted attention in biomedical field because of their biocompatibility, flexibility and similarity to natural tissues, etc. Poly(vinyl alcohol) (PVA) is a water-soluble and biocompatible polymer, which has been applied in a variety of biomedical fields. In chapter 1, recent progresses in PVA-based hydrogel are reviewed.High-generation dendrimer could be viewed unimolecular micelle, as a result, it showed "unimolecular encapsulation" behavior. High-generation dendrimer can be regarded as a new kind of host molecule and used in drug delivery. In chapter 2 and 3, arnino-terminated and hydroxy-terminated polyamidoamine(PAMAM) dendrimers (G6-NH2 and G6-OH) were introduced into PVA to form novel physically cross-linked hydrogels by freezing-thawing methods. Compared with physically cross-linked PVA hydrogel, PVA/PAMAM dendrimer hydrogels show higher swelling ratios and faster reswelling rate. Higher contents of PAMAM dendrimer in PVA/PAMAM dendrimer hydrogels resulted in higher swelling ratios and faster reswelling rates. With increasing freezing/thawing cyclic times, the swelling ratios and reswelling rates of PVA/PAMAM dendrimer hydrogels decreased. When temperature rise, the reswelling rates of PVA/PAMAM dendrimer hydrogels increase. The in vitro release of 5-Fu indicated that the introduction of PAMAM dendrimer into PVA hydrogel enlarged the drug-loading amounts of 5-Fu in the hydrogels and prolonged the drug release time.Xanthan gum is a natural polysaccharide. It possesses large amounts of functional groups and shows low cytotoxicity. In chapter 4, we introduced xanthan gum into PVA to prepare physically cross-linked PVA/ xanthan gum hydrogels by freezing-thawing methods. Compared with physically cross-linked PVA hydrogel, PVA/xanthan gum hydrogels show higher swelling ratios and faster reswelling rate. With the increase of xanthan gum contents in PVA/xanthan gum hydrogels, the swelling ratios andreswelling rates of PVA/ gum xanthan hydrogels increased. With increasing freezing/thawing cyclic times, the swelling ratios and reswelling rates of PVA/xanthan gum hydrogels decrease.Poly(N-isopropylacrylamide) (PNIPA) hydrogel is a typical thermosensitive hydrogel with a lower critical solution temperature(LCST) around 33癈. PNIPA hydrogel has been utilized in many fields, such as drug release, enzyme immobilization and molecular separation. However, the responsive rate of conventional PNIPA hydrogel to the enviromental temperature change is very slow. In chapter 5, we report the preparation and characterization of semi-IPN PNIPA/xanthan gum hydrogels. PNIPA/xanthan gum hydrogels show similar LCST at about 33癈. When the contents of xanthan gum in PNIPA/gum xanthan hydrogel increase, the swelling ratios of PNIPA/ xanthan gum hydrogel siganificantly increase, the deswelling rates and reswelling rates of PNIPA/ xanthan gum hydrogel become faster.Gene delivery system is one of components of a gene medicine, which deliver the therapeutic gene to the desired location of the body. For in vivo gene therapy, It is a challenge to develop safe and efficient gene carriers. In general, gene delivery systems include viral and nonviral carriers. Viral vectors have high transfection efficiency, however, the safety problem limit the application of viral vectors in human gene therapy. Nonviral vectors offer advantages over viral system of safety, ease of manufacturing, etc, which have greatly attracted the attention in the past two decades. Cationic Polymers are important nonviral gene delivery vectors. In chapter 6, the fundamental and recent progresses of cationic polymer-based gene delivery vectors are reviewed.To date, polyethylenimine(PEI) is the most successful cationic polymer gene delivery vector. PEI showes high transfection efficiency, however, it is highly toxic and undegradable...