Preparation Of Thermo-responsive Glycopolymer Nanofibers And Their Sustained Release Of Drugs

Nano-drug delivery system is such a kind of system which is prepared from numerous materials and whose diameter size is between50～1000nm. Drugs can be entrapped or dissolved into nanosystems, or be absorbed/scattered on the surface of systems. Nano-drug delivery systems can change the drug distribution in vivo, improve drug dissolution rate, enhanced drug property of targeting, controlled releasing, controllability, low toxicity and intelligent, so that drugs can play a better therapeutic effect or diagnostic function in medical part. Such multitude excellent performance makes nano-drug delivery system become a hot direction on drug modification research in recent decades.In nano-drug delivery systems, the intelligent materials occupy an important position because of its unique biomimetic properties. Lately, Poly (N-vinyl caprolactam)(PNVCL), the thermo responsive polymer, is attracting considerable attention from many researchers. This material has a phase transition temperature in the range of30～40℃(likes PNIPAM known to all), which is very close to the physiology temperature of human. Due to its high coordination properties, the material also owns complexation ability with different organic compounds and biocompatibility in vivo. After hydrolysis, it doesn’t product toxic amino derivatives compared to PNIPAM.The paper selected ferulic acid vinyl ester as the model drug, to develop a simple and convenient preparation nano drug delivery system (nanofibers) containing thermo-responsive comonomer NVCL. Drug-loaded nano-fibers, containing thermo-responsive N-vinyl caprolactam (NVCL), were prepared by free radical polymerization. Their structure and morphology were confirmed by a variety of character means; the relationship during structure, morphology and nature of two nano-drug delivery system were researched. The potential application of the material was confirmed by temperature-sensitive tests and biological characteristic tests. Its morphology of drug-loaded thermal sensitive nanofibers was determined by means of scanning electron microscopy. The main research could be summarized as follows:(1) Comonomers (Feruic acid vinyl ester,6-O-vinylsuccinyl-α-D-galactose (OVSG),6-O-vinylnonanedioyl-α-D-galactose (OVNG) were synthesized by chemical and enzymatic methods respectively. Two novel thermo-responsive copolymers, Poly (OVSG-co-NVCL) and Poly (OVNG-co-NVCL), were prepared by free radical polymerization. FT-IR,1H NMR and other analytical methods confirmed products’ compound characterization. For Poly (OVSG-co-NVCL) and Poly (OVNG-co-NVCL) with different monomer ratios, molecular weights were confirmed by gel permeation chromatography (GPC). The lower critical solution temperature (LCST) of the copolymer was verified by UV-visible spectrophotometer.The results showed that:a) Poly (OVSG-co-NVCL) and Poly (OVNG-co-NVCL) with different monomer ratios all had high molecular weight and narrow dispersion,1H NMR analysis suggested drug loading content of Poly (OVSG-co-NVCL) and Poly (OVNG-co-NVCL) could be effectively controlled through regulating monomer ratio. LCSTs of Poly (OVNG-co-NVCL) were between30～42℃, well LCSTs of Poly (OVSG-co-NVCL) were between42～60℃. So Poly (OVNG-co-NVCL) can be agglomerate not loose on human physiological temperature. LCSTs of Poly (OVNG-co-NVCL) with different monomer ratios displayed that higher value of LCST with higher sugar content. When the sugar content reaches a certain amount in copolymer, LCST no more exists. With sugary copolymer monomer ratio increases, the specific molecular structure conformation NVCL greater impact, leading to its hydrophilic/hydrophobic there is a greater change.Due to the experiment requirements, we selected copolymer (ⅰ) with suitable LCST as materials for next experment, to ensure that the material will be not immediately dissolved in aqueous solution. GPC of copolymer (ⅰ) also showed that it has a high molecular weight and narrow dispersion for electrospun.(2) In this thesis, biological characteristics of temperature-sensitive materials were studied. Lectin recognition experiments conducted and MTT assay was carried on with prepared thermosensitive material Poly (OVSG-co-NVCL) and Poly (OVNG-co-NVCL). By lectin recognition experiments, Poly (OVNG-co-NVCL) seems to own better biometric features than Poly (OVSG-co-NVCL), so MTT assay was carried on with Poly (OVNG-co-NVCL) for biocompatibility evaluation. Hella cells was chosen as a detection matrix, it resulted as Poly (OVNG-co-NVCL) has good biocompatibility, relatively smaller side effects and promotes cell growth. This material is used in wound dressings not only has anti-inflammatory effect but also conducive to rapid wound healing.(3) Ferulic acid sugar ester-loaded Poly (OVNG-co-NVCL) nanofibers were successfully prepared by electrospinning method in ethanol solutions as the spinning solutions. The fabrication parameters were determined by SEM, DSC and XRD measurements. SEM was carried out to observe the morphology of the nanofibers. DSC and XRD were conducted to clarify the states of the drug. Drug release profiles were investigated using in vitro dissolution tests under different temperature conditions. Results from SEM showed that the drug was distributed evenly in Poly (OVNG-co-NVCL) nanofibers. DSC and XRD results showed that ferulic acid vinyl ester dispersed in Poly (OVNG-co-NVCL) with Noncrystalline. In vitro release study showed that temperature influenced the drug release pattern from nanofibers. As expected, the rate and amount of drug release was found to be much faster below the LCST than that above the LCST of Poly (OVNG-co-NVCL). At20℃, about80%of the drug was released within6h; it released almost all in8h. In contrast, at40℃, the drug release from the nanofibers was characterized with an initial burst (approximately0-20%of the initial loading amount) followed by a sustained release (approximately20-40%of the initial loading amount) and a nonrelease phase (beyond60%of the initial loading amount).