Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea.
Department of Surgery, Chonnam National University Medical School, Gwangju 61469, Korea.
Mar Drugs. 2019 Jan 10;17(1):41. doi: 10.3390/md17010041.
In this study, we prepared an injectable drug delivery depot system based on a visible light-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin (β-CD) (GC/CD/PTX) for ovarian cancer (OC) therapy using a tumor-bearing mouse model. The hydrogel depot system had a 23.8 Pa of storage modulus at 100 rad/s after visible light irradiation for 10 s. In addition, GC was swollen as a function of time. However, GC had no degradation with the time change. Eventually, the swollen GC matrix affected the releases of PTX and CD/PTX. GC/PTX and GC/CD/PTX exhibited a controlled release of PTX for 7 days. In addition, GC/CD/PTX had a rapid PTX release for 7 days due to improved water solubility of PTX through CD/PTX complex. In vitro cell viability tests showed that GC/CD/PTX had a lower cell viability percentage than the free PTX solution and GC/PTX. Additionally, GC/CD/PTX resulted in a superior antitumor effect against OC. Consequently, we suggest that the GC/CD system might have clinical potential for OC therapy by improving the water solubility of PTX, as PTX is included into the cavity of β-CD.
在这项研究中,我们制备了一种基于可见光固化的壳聚糖(GC)水凝胶的可注射药物输送库系统,该水凝胶中含有紫杉醇(PTX)-β-环糊精(β-CD)复合物(GC/CD/PTX),用于使用荷瘤小鼠模型进行卵巢癌(OC)治疗。水凝胶库系统在可见光照射 10 秒后,在 100 rad/s 下具有 23.8 Pa 的存储模量。此外,GC 随时间而溶胀。然而,GC 随时间变化没有降解。最终,溶胀的 GC 基质影响了 PTX 和 CD/PTX 的释放。GC/PTX 和 GC/CD/PTX 表现出 7 天的 PTX 控制释放。此外,由于通过 CD/PTX 复合物提高了 PTX 的水溶性,GC/CD/PTX 在 7 天内迅速释放 PTX。体外细胞活力测试表明,GC/CD/PTX 的细胞活力百分比低于游离 PTX 溶液和 GC/PTX。此外,GC/CD/PTX 对 OC 具有更好的抗肿瘤作用。因此,我们建议 GC/CD 系统通过提高 PTX 的水溶性,将 PTX 包含在 β-CD 的腔中,可能具有 OC 治疗的临床潜力。