Structure, Property Characterization And Sustained-controlled Ibuprofen Delivery Of Functionalized Stimuli Responsive Polymer Materials

The research and development of novel drug carriers is one of the main topics on the improvement of traditional chemotherapy and clinical use of drugs. Because of complexity of biological environments, lots of drug carriers with good compatibility and biodegradability must have a special functionality of targeting release and tracking release of drugs, besides that the sustained-drug delivery properties and feasibility. In which, the functional copolymers with oriented design and controlled preparation is one of the hot issues for current researches. Particularly, pH-stimuli copolymer containing carbonoxy groups can be aware of the pH varieties of physicochemical environments, which is beneficial to realize the drug targeting release. However, the influences of various parameters including cation concentration and strength on the pH-responsibility are very remarkable. Meanwhile, in recent years,the fluorescent labels copolymers presented several problems such as poor compatibility, toxicity, complicated surface modification, and thereby their biodegradable autofluorescence performances need to be addressed in-depth.Therefore, on the basis of previous work in our group, the salt tolerance for pH-sensitivity copolymers was investigated in this dissertation. Meanwhile, the atuofluorescence copolymers were synthesized and their fluorescence performance in the drug loading and drug release behaviors were also explored. The main contents are summarized as follows:1. The pH-sensitivity Dextran-Poly(acrylic acid) copolymers(D-A) have been prepared via free-radical solution polymerization of acrylic acid and dextran which has good biodegradable. Ibuprofen(IBU) was applied as the model drug, the effect of ionic strength(Ca2+, Na+) and ionic concentration(0.05M-0.2M NaCl) on IBU-release behavior from D-A copolymer were investigated in detail. The results showed that the balance cumulative release of IBU decreased with the increase of ionic strength and ionic concentration, this fully explained the obtained Dex-PAA have tolerance to salt solution. Meanwhile, the influences of different salt species and different Na+concentrations on Zeta potential and particle distribution of D-A copolymer were investigated, which explained the mechanism of salt ionic effect on drug release.2. The autofluorescence poly(ethylene glycol)-co-(lactic acid) diacrylate(PPA)copolymers was prepared by lactic acid and biodegradable poly(ethylene glycol).Meanwhile, the effect of the molar ratio of acryloyl chloride and poly(ethylene glycol)-co-(lactic acid) on fluorescence performance of obtained copolymers were investigated. The results showed that PPA have a good autofluorescence property,meanwhile, with an increase in the acylation efficiency, the characteristic fluorescence emission peak had a red-shift from 455 nm to 487 nm. Moreover, theconcentration of PPA-n copolymer can effect the emission peak position and intensity,with the decrease of concentration, the emission peak shifted to lower value, and the fluorescence quenching phenomenon would be weakened, thus the intensity of emission peak increased. In addition, the monodisperse experiments furtherly indicated that the acylation effieciency and distribution have apparent impact on the fluorescence property.3. Using IBU as a model drug, the different drug loading methods were chosen to investigated the effect on the drug-loading amount. The results showed that different ways of drug-loaded micelle formation is the main reason affecting the drug-loading amount. Meanwhile, with the increase of acylation efficiency of AC, the copolymer had higher drug loading amount. Moreover, the particle size of IBU-loaded and IBU-released copolymers was investigated. The results demonstrated that the particle size of micelles had an apparent increase with an increase of acylation efficiency and loading amount. Moreover, the release rate decreased remarkably with an increase of acylation efficiency. In addition, the fluorescence properties of IBU-loaded and IBU-released copolymers suggested that PPA-n could be promising for fluorescence labeling and drug delivery applications.4. All the copolymers and related drug loaded samples were characterized by means of Fourier transform-infrared spectroscopy(FT-IR); thermogravimetric analyses(TGA); Proton nuclear magnetic resonance spectroscopy(1HNMR); X-ray diffraction(XRD); scanning electron microscopy(SEM); Particles/Zeta potential analysis; UV-vis spectra; High performance liquid chromatography(HPLC);Fluorescence spectrometer and Time-resolved fluorescence spectrometry.