College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Institute of High Performance Polymers, Qingdao University of Science and Technology, Qingdao 266042, China.
College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; Institute of High Performance Polymers, Qingdao University of Science and Technology, Qingdao 266042, China.
J Pharm Sci. 2023 Jul;112(7):1863-1871. doi: 10.1016/j.xphs.2023.02.004. Epub 2023 May 16.
A triblock copolymer was synthesized by ring opening polymerization of ε-caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.
嵌段共聚物是通过在聚乙二醇（PEG）存在的情况下，ε-己内酯的开环聚合而合成的。所得的 PCL-PEG-PCL 三嵌段共聚物、PEG 和单甲氧基（MPEG）通过端基丙烯酰化进行功能化。NMR 和 FT-IR 分析证明了聚合物的成功合成和功能化。通过使用苯基亚膦酰二苯基作为引发剂，用可见光照射，制备了由丙烯酰化 PEG-PCL-Acr 和 MPEG-Acr 或 PEG-Acr 组成的一系列光交联水凝胶。SEM 显示水凝胶具有多孔和相互连接的结构。水凝胶的溶胀性能与交联密度和亲水性含量密切相关。添加 MPEG 或 PEG 会导致水凝胶的吸水能力增加。在猪胰腺脂肪酶存在下，实现了水凝胶的体外降解。获得了各种降解速率，主要取决于水凝胶的组成。MTT 测定证实了水凝胶的良好生物相容性。重要的是，通过辐照注入小鼠腹部的前体溶液实现了原位凝胶化。阿霉素（DOX）被选为模型抗肿瘤药物，以评估水凝胶在癌症治疗中的潜力。通过原位包封制备载药水凝胶。体外药物释放研究表明，在 28 天内持续释放，具有较小的爆发释放。载药水凝胶对 A529 肺癌细胞表现出与游离药物相当的抗肿瘤活性，表明具有可调节性质的可注射原位水凝胶可能最有希望用于癌症治疗中的局部药物递送。
