Synthesis And Properties Of X-ray Radiopaque Iodinated Poly(lactic Acid)Interventional Embolization Materials

X-ray imaging technology is not only the most commonly used diagnostic method in clinical medicine,but also the main tracer technology in interventional therapy.In the minimally invasive surgery of interventional therapy,radiopaque materials can be implanted into a designated position through a catheter,and track its location in a non-invasive way in post-operation.Many kinds of radiopaque polymers have been synthesized,although polylactic acid(PLA)is the most widely used and most promising biodegradable polymer material,it is still difficult to obtain the radiopaque PLA because PLA lacks the reactive site for introduction of iodinated groups,it is a high value research to synthesis of the radiopaque PLA materials.The synthesis of the radiopaque PLA materials will further broaden the types of the radiopaque materials,with high practical significance.In this dissertation,three kinds of synthetic methods,"end-chain functionalization method","in-chain functionalization method”,and”chain extension method",were used to synthesize a series of I-PLA materials with different molecular structure.The effects of iodine on the structure and properties of PLA were investigated.The application prospect of I-PLA in the field of interventional embolization agent was also disscussed.The main contents and results were summarized as follows:1)Two different molecular structures I-PLA were synthesized by "end-chain functionalization method",this series of I-PLA could regulate the iodine content and radiopaque performance of the polymer through the length of molecular chain.The effects of TIB A on the radiopaque performance and crystallization ability of PLA were investigated.The I-PLA microspheres were prepared by "O/W method" and the in vitro cytotoxicity of I-PLA microspheres were evaluated;the degradation behavior of I-PLA microspheres and the attenuation of radiopaque performance during degradation were specially investigated.The results show that the bulky iodine atom in TIBA limited the structural regularity of the molecular chain,thus inhibiting the crystallization ability of PLA in a certain extent.The Micro-CT test shows that this series I-PLAs has a high HU value which could afford clear CT images.The radiopacity ability of the materials increases with the increase of the TIBA content in PLA.The sample I-S-PLA8k has the best imaging performance.The series of I-PLA microspheres kept high HU values and excellent clear CT imaging results during the three-month degradation process.2)A series of high-branched I-PLAs were synthesized by "end-chain functionalization method".High-branched PLAs were firstly synthesized by linear hydroxylated polybutadiene as macroinitiator,and then esterification with TIBA.This series of I-PLAs has more reactive sites(terminal hydroxyl groups)than the linear two-arm and star four-arm structure PLAs,which could afford high HU value with high molecular weight.The microspheres prepared by these series of I-PLAs were non-cytotoxic and biocompatible,with uniform particle size,good dispersion and roundness,which could be used as a long-term embolization and exhibited great potential in theranostic applications.3)A series of I-PLA copolymers were synthesized by "in-chain functionalization".The I-PLA copolymer was synthesized by a combination of functional monomer and ring-opening copolymerization with lactide and oxime "click" postfunctionalization.The iodine content and radiopaque performance of the iodinated copolymer could be regulated by the monomer placement ratio,which could be more flexible.This series of I-PLA materials can provide clear images under both X-ray and CT equipment.In terms of biological evaluation,this series of materials can well support the growth and proliferation of mouse embryonic fibroblasts(3T3),and this series of materials did not cause obvious inflammatory reaction in the implanted organization during 4 weeks,indicating that the material has both good biocompatibility and biodegradability in the highly controllable radiopaque performance.It is preliminarily confirmed that this series of I-PLA materials exhibited potential application in the field of interventional embolic agents.4)Diiodoneopentyl glycol(I-NPG)was synthesized as a new type of chain extender.There were three kinds of iodine-containing polyurethane(I-PU)with radiopaque function,which synthesized by different soft segment structures,polylactic acid-based polyurethane,polycaprolactone-based polyurethane and polylactic acid-polycaprolactone-based polyurethane.The effect of polymer properties in the same soft segment component before and after the iodinated was been compared.A series of I-PU/DOX drug-loaded microspheres were prepared by the "W/O/W method",and the partical size was evenly distributed in 50?m-400?m;the microspheres has high drug loaded and sufficient drug release ability,with a cumulative release rate of over 80%in a two-month release cycle.This series of I-PU has a high HU value and good embolization performance,with clear X-ray and CT images.It could successfully embolize rabbits' hepatic arteries,and can provide good CT imaging tracking performance after embolization.It is a kind of X-ray radiopaque drug-lording microsphere with great potential for chemo-therapy applications...