Functional Modification And Molecular Simulation On Biodegradable Aliphatic Polycarbonate

Degradable polymer for medical materials has a great interesting potential. Aliphatic polycarbonate is a kind of biodegradable and biocompatible polymer with good flexibility. And a little fractional acidic substance is released during degradation of the polymers. Hence, aliphatic polycarbonate for loading-drug materials has an attractive future, and has been given much attention and recognition by many researchers. At present, the most reported researches are focused on how to promote the efficiency of polymerization and activity of catalysts. As comes to the functionality, however, the work about the modification of properties needs further research and development.Therefore, in this paper, the work focused on how to enhance the functionality of aliphatic polycarbonate. A novel aliphatic polycarbonate was successfully achieved with third monomer, which greatly modified the non-enzymatic degradability and drug-loading and release properties. Blending with hydrophilic polymers, its functionality was strengthened. Based on experiments, the relationship between microstructure and macroscopical properties of the polymer was investigated using molecular simulation. The selective distribution of drugs in the system was observed in the computer simulation. The characteristic endues the polymer with remarkable researchful worthiness. The main research can be summarized as following.A novel aliphatic poly (propylene-co-γ-butyrolactone carbonate) (PPCG) was firstly successfully achieved by anionic complexation polymerization, which was the polymerization product of carbon dioxide (CO₂), propylene oxide (PO) and γ-butyrolactone (GBL). Through optimizing the reaction factors, the PPCG with abundant CO₂ and GBL units was obtained.Because of the complicacy of tri-system, it is hard to deduce the compositive function usually. Based on the copolymerization mechanism of binary system, the copolymerization mechanism was investigated about the CO₂, PO and GBL tri-system. The reactivity ratios of monomers and composition equation of copolymer were computed. The molecular structure of PPCG was detailedly analyzed. Both results of theory and experiment of spectroscopic analysis mutually support each other.The thermal properties of PPCG were characterized. The effect of GBL on the thermal stability of PO-CO2 molecule bond was studied. The manner, dynamics and mechanism of PPCG thermo-oxidative degrade-ation were thoroughly discussed. It was found that the apparent active energy of its thermo-oxidative degradation was 97.8-104.77 KJ/mol. And the thermo-oxidative degradation kept to one dimension phase- boundary mechanism. The work has been reported on a SCI-source journal.With increasing GBL content, the hydrophilicity and non-enzymatic degradability of PPCG were improved. The degradation speed of PPCG is more than 8 times of that of PPC. The degradation speed of PPCG can be adjusted by controlling the GBL content. The pH of environment has a great influence on degradative behavior of PPCG. The character makes PPCG hopeful for being applied as an oral drug-carrier, which can avoid the erosion of acidic environments (such as stomach) in body, but release drug at alkaline environments (such as intestines). Hence it is potential to effectively resolve invalidation of drug under acidic environment.PPCG microspheres were prepared by the (W/0)/W multiple emulsions method. The factors, which could obviously impact on the carried-drug capability of PPCG, were studied systematically. The PPCG-glucose microspheres were obtained with smooth and spherical surface. The drug loading and encapsulation efficiency were up to 43% and 84% respectively. The outcome offers an instructive inspiration on studying PPCG microspheres with soluble and low molecular drug.The O/W emulsion method was used for PPCG-caffeine microspheres. The PPCG-caffeine microspheres were obtained with smooth and spherical surface, and 519nm in diameter. The encapsulation efficiency was up to 94% with high initial brush and release speed. The effect of caffeine on degradative behavior of PPCG was discussed. In PPCG-caffeine microspheres, caffeine mainly plays a role as the alkaline catalyst and enhances the degradability of PPCG. The outcome offers an important basis on studying PPCG microspheres with insoluble drug, and expatiating on the influence of alkaline drug on the material.With combining the molecular informatics of extender and synthetic, the reciprocities between PPCG and extenders, such as starch and polyethylene glycol (PEG), were studied. Starch enhanced the thermal stability, hydrophilicity and degradability of PPCG largely. The PPCG-starch blends possessed stronger degradability in either alkaline oracid environments. Moreover, alkali tended to destroy the blend structure of PPCG-starch rather than acid. When PPCG:PEG = 2:1, the thermal stability of the blends was increased to the fullest extent. PPCG changed the phase change state of PEG with good solid-solid phase- transition character. The hydrophilicity and degradability of PPCG-PEG blends was enhanced with increasing PEG content. The PEG particles in the PPCG-PEG blends became the erosive points, which made the blends excellent degradability in both acid and alkaline media. It is just the essential for increasing the degradation speed of the PPCG-PEG blends. The result offers a new thought on exploration blending and intrinsic mechanism of degradation of PPCG blends.It is firstly reported in this paper that the preparation of PPCG-PEG microspheres carried bovine serum albumen (BSA) was studied with the (W/O)/W multiple emulsions method. With enhancing the hydrophilicity of PPCG-PEG microspheres the diameter increased, while loading efficiency and encapsulation efficiency decreased. In the initial phase of drug release, the dissolution of PEG plays the dominating role. Without obvious lag period, the release process of PPCG-PEG carried BSA microspheres is first-order release kinetics in 30 days. The release speed increased with the increase of PEG content. The outcome offers an important basis on possibility and technique of PPCG-PEG blending microspheres with soluble and high molecular drug.Based on the Compass force field, the systems of PPCG, PPCG-caffeine, PPCG-PEG, and PPCG-Starch were firstly simulated by the 'Materials Studio' soft. The interactions among three monomers and caffeine, PEG and starch were investigated. The existent states of molecules were probed into. The results of molecular simulation not only hold the experimental conclusions, but also obtained clarification and comprehension of the relationships between molecular structure and macroscopical properties of PPCG.