Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699-5810, USA.
Department of Biology, Clarkson University, Potsdam, NY, 13699-5805, USA.
Macromol Biosci. 2020 May;20(5):e1900377. doi: 10.1002/mabi.201900377. Epub 2020 Mar 23.
The correlation between erosion and drug (lidocaine and 6-mercaptopurine, 6-MP) release from amorphous poly(thioether anhydrides), which are synthesized using radical-mediated thiol-ene polymerization, is reported. Cytotoxicity studies of the polymer toward human fibroblast human dermal fibroblasts adult, melanoma A-375, and breast cancer MCF-7 cells are conducted, and drug efficacy of a cancer and autoimmune disease drug (6-MP) when released from the poly(thioether anhydrides) is examined against two cancerous cell types (A-375 and MCF-7). Erosion and drug release studies reveal that lidocaine release is governed by network erosion whereas 6-MP is released by a combination of erosion and diffusion. The cytotoxicity studies show that all three cell types demonstrate high viability, thus cytocompatibility, to poly(thioether anhydrides). Toxicity to the material is dose dependent and comparable to other polyanhydride systems. The 6-MP cancer drug is shown to remain bioactive after encapsulation in the poly(thioether anhydride) matrix and the polymer does not appear to modify the efficacy of the drug.
报道了通过自由基介导的硫醇-烯聚合合成的无定形聚硫醚酸酐中侵蚀与药物（利多卡因和 6-巯基嘌呤，6-MP）释放之间的相关性。对聚合物对人成纤维细胞、人真皮成纤维细胞、黑色素瘤 A-375 和乳腺癌 MCF-7 细胞的细胞毒性进行了研究，并研究了从聚硫醚酸酐释放的癌症和自身免疫性疾病药物（6-MP）对两种癌细胞类型（A-375 和 MCF-7）的药效。侵蚀和药物释放研究表明，利多卡因的释放受网络侵蚀控制，而 6-MP 的释放则是侵蚀和扩散的结合。细胞毒性研究表明，所有三种细胞类型均表现出高活力，因此对聚硫醚酸酐具有细胞相容性。材料的毒性与其他聚酸酐系统相当，且呈剂量依赖性。包裹在聚硫醚酸酐基质中的 6-MP 癌症药物仍保持生物活性，且聚合物似乎不会改变药物的疗效。
