Polymer Degradation and Stability ( IF 5.9 ) Pub Date : 2018-04-10 Martina Fabbri, Giulia Guidotti, Michelina Soccio, Nadia Lotti, Marco Govoni, Emanuele Giordano, Massimo Gazzano, Rita Gamberini, Bianca Rimini, Andrea Munari
A series of random poly(butylene succinate)-based copolymers, (poly(butylene/triethylene succinate) (P(BSmTESn)), containing ether-oxygen atoms were successfully synthesized by melt polycondensation of succinic acid and 1,4-butanediol in the presence of triethylene glycol (TEG) (TEG content up to 40 mol%). The copolymers were characterized from the molecular, thermal, structural and mechanical point of view. Hydrolytic degradation studies were performed under physiological conditions. The biocompatibility of the samples under investigation through indirect and direct biocompatibility studies was investigated by using embryonic rat cardiac H9c2 cells. To evaluate the potential of these polymers also for controlled drug delivery systems, the diffusion profile of Dexamethasone, an anti-inflammatory drug, through nanoparticles prepared by oil-in-water miniemulsion process was investigated. Results showed that solid-state properties could be tailored nicely by simply varying copolymer composition. Crystallinity degree and hydrophobicity significantly decreased with the increase of triethylene succinate co-unit (TES) mol%. Moreover, hydrolytic degradation of PBS, depending on polymer crystallinity degree and hydrophilicity, was remarkably improved: the copolymer containing 40 mol% of triethylene succinate co-unit after 200 days lost over 22% of its initial weight. The newly developed biomaterials showed lack of cell cytotoxicity. Among them, PBS and the copolymers containing up to 20 mol% of TES co-units sustained a better cell adhesion and proliferation. In addition, such copolymers induced muscle phenotype commitment in H9c2 cells cultured onboard. Lastly, the release profile of Dexamethasone obeyed to a first order kinetic law, the copolymer richest in TES co-unit content showing the highest encapsulation capability and the fastest drug release kinetics. Anyway, PBS and the copolymers containing up to 20 mol% of TES co-unis sustained a better cell adhesion and proliferation, with the copolymers characterized by a myosin heavy chain expression, which appeared to be up to twofold increased on respect to the one of PBS homopolymer.
中文翻译:
新型可生物相容的基于PBS的包含PEG-like序列的无规共聚物,可用于生物医学应用:从药物递送到组织工程
通过水包油细乳液工艺制备的纳米颗粒的研究。结果表明,只需改变共聚物组成,即可很好地调节固态性能。结晶度和疏水性随琥珀酸三乙烯酯共单元(TES)mol%的增加而显着降低。而且,取决于聚合物结晶度和亲水性,PBS的水解降解得到显着改善:在200天后,含有40mol%三亚乙基琥珀酸酯共单元的共聚物损失了其初始重量的22%以上。新开发的生物材料显示缺乏细胞毒性。其中,PBS和包含高达20mol%的TES共单元的共聚物保持了更好的细胞粘附和增殖。此外,此类共聚物在船上培养的H9c2细胞中诱导了肌肉表型的定型。最后,地塞米松的释放曲线符合一级动力学定律,TES单元含量最丰富的共聚物显示出最高的包封能力和最快的药物释放动力学。无论如何,PBS和含高达20 mol%TES co-unis的共聚物保持了较好的细胞黏附和增殖,其共聚物的特征是肌球蛋白重链表达,相对于其中一种,其表达增加了近两倍。 PBS均聚物。