| Recently, along with the development of medical image systems such as X-ray apparatus, radiopaque materials are widely used in interventional operation for the location of implants as well as in post-operation for the evaluation of implants. Unfortunately, conventional polymeric biomaterials such as polyurethanes cannot be detected by X-ray, so the strategies to develop radiopaque polyurethanes are of great importance to diversify the synthetic embolic materials in interventional therapy. In this thesis, a series of radiopaque iodinated polyurethanes which differ in soft segment chemistry were synthesized via "iodinated chain-extending method". Three different diols, namely, poly butylene succinate (PBS), polycaprolactone (PCL) and polylactide (PLA) were used for this purpose. Radiopacity was introduced into the polyurethane by covalent bonding with iodinated Bisphenol A (IBPA) as chain extender and X-ray contrast. The effects of iodine atoms on chemical structure and properties of polymers were specially discussed, and the potential application of embolic agents was also investigated. The main contents were summarized as follows:1) A series of iodinated PBS-based polyurethanes (I-PBSU) and non-iodinated PBS-based polyurethane (PBSU) were synthesized for comparison. The effects of iodine atoms on structure and properties of I-PBSU were investigated. The analysis of crystallization showed that bulky iodine atoms leading to the retarded crystallization of I-PBSU and transformed from ring-band spherulites to irregular texture. It is also found that I-PBSUs exhibited complicated multiple melting behavior, which can be explained by the twice sequential melting-recrystallization model. The primary crystals formed at isothermal crystallization stage undergo a metastable phase and finally transformed into the thermodynamically stable state. These results revealed the relationship between the aggregation structure and properties.2) A series of iodinated PCL-based polyurethanes (I-PCLU) and the non-iodinated polyurethanes (PCLU) were synthesized. The effects of IBPA chain extender on degradation behavior and the attenuation of X-ray opacity of I-PCLU were specially investigated. Also, the anti-tumor effect of I-PCLU drug-loaded microspheres were investigated. The enzymatic degradation study indicated that the in-vitro degradation of I-PCLU were greatly hindered because of the steric hindrance of iodine atoms. On the other hand, iodine atoms were firmly anchored on the chain of polyurethanes, therefore the radiopacity of I-PCLU with clear X-ray visibility did not sharply attenuated during the enzymatic degradation. Moreover, the drug-loaded I-PCLU/DOX microspheres with homogenous drug distribution, exhibited a slow-release effect and effective anti-tumor effect in vitro. Above all, the investigations of degradation, X-ray attenuation as well as drug-loaded microspheres of iodinated polyurethanes laid a good theoretical foundation on supporting the application of embolic agents.3) Six iodinated PLLA-based polyurethanes (I-PLAU) were synthesized and characterized. As the increased molecular weight of PLLA-OH. the crystallization and thermal stability increased. On the other hand, as the increase amount of IBP A, the crystallization was restrained and thermal stability were slightly decreased, however, the radiopacity was greatly enhanced. Also, I-PLAU exhibited highly radiopacity, coagulation capacity, as well as good in-vitro/in-vivo biocompatibility and biodegradation. Moreover, I-PLAU showed great potential in drug delivery, and the drug release behavior of I-PLAU/DOX microspheres exhibited a slow-release effect, which was agreed with the biphase kinetic function. In conclusion, it is confirmed that biodegradable X-ray radiopacity has a great potential in embolization. |
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