School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Department of Cell Biology, Second Military Medical University, Shanghai 200433, China.
Molecules. 2022 Sep 3;27(17):5690. doi: 10.3390/molecules27175690.
To improve the antitumor effect of combined capecitabine (CAP) and osimertinib (OSI) therapy and quickly and efficiently reduce tumor volumes for preoperative chemotherapy, we designed a compound CAP colon-targeted microparticle (COPMP) prepared by coaxial electrospray. COPMP is a core-shell microparticle composed of a Eudragit S100 outer layer and a CAP/OSI-loaded PLGA core. In this study, we characterized its size distribution, drug loading (DL), encapsulation efficiency (EE), differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, formula ratio, cellular growth inhibition, and in vivo antitumor efficacy. COPMP is of spherical appearance with a size of 1.87 ± 0.23 μm. The DLs of CAP and OSI are 4.93% and 4.95%, respectively. The DSC showed that the phase state of CAP and OSI changed after encapsulation. The FTIR results indicated good compatibility between the drug and excipients. The release curve showed that CAP and OSI were released in a certain ratio. They were barely released prior to 2 h (pH 1.0), less than 50% was released between 3 and 5 h (pH 6.8), and sustained release of up to 80% occurred between 6 and 48 h (pH 7.4). CAP and OSI demonstrated a synergistic effect on HCT-116 cells. In a colon tumor model, the tumor inhibition rate after oral administration of COPMP reached 94% within one week. All the data suggested that COPMP promotes the sustained release of CAP and OSI in the colon, which provides a preoperative chemotherapy scheme for the treatment of colon cancer.
为了提高卡培他滨(CAP)和奥希替尼(OSI)联合治疗的抗肿瘤效果,并快速有效地缩小肿瘤体积以进行术前化疗,我们设计了一种通过同轴电喷雾制备的复合 CAP 结肠靶向微粒(COPMP)。COPMP 是一种由 Eudragit S100 外层和载有 CAP/OSI 的 PLGA 核组成的核壳微粒。在这项研究中,我们对其粒径分布、载药量(DL)、包封效率(EE)、差示扫描量热法(DSC)、傅里叶变换红外光谱(FTIR)、体外释放、配方比、细胞生长抑制和体内抗肿瘤功效进行了表征。COPMP 呈球形,粒径为 1.87±0.23μm。CAP 和 OSI 的 DL 分别为 4.93%和 4.95%。DSC 表明 CAP 和 OSI 的相态在包封后发生了变化。FTIR 结果表明药物与赋形剂之间具有良好的相容性。释放曲线表明 CAP 和 OSI 以一定比例释放。在 pH 1.0 下,它们在 2 小时前几乎不释放,在 pH 6.8 下 3 至 5 小时之间释放不到 50%,在 pH 7.4 下持续释放高达 80%。CAP 和 OSI 对 HCT-116 细胞表现出协同作用。在结肠肿瘤模型中,COPMP 口服给药一周后肿瘤抑制率达到 94%。所有数据表明,COPMP 促进 CAP 和 OSI 在结肠中的持续释放,为结肠癌的治疗提供了术前化疗方案。