Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, 51452, Kingdom of Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.
Sci Rep. 2020 Mar 13;10(1):4736. doi: 10.1038/s41598-020-61605-y.
There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.
需要开发一种针对结直肠癌的口服型西妥昔单抗（CTX）药物，因为结直肠癌被报道表达生长抑素受体（SSTRs）。因此，将 CTX 与生长抑素类似物（如奥曲肽（OCT））结合起来进行包裹是有益的。海藻酸钠被用于包裹 CTX 以促进其递送至胃肠道（GIT）。本研究旨在以微颗粒的形式递呈 OCT 偶联的 CTX，作为一种 GIT 靶向的 SSTR 治疗方法。CTX 和 OCT 均采用溶剂蒸发法进行偶联，然后将偶联的 CTX-OCT 载入 Ca-海藻酸钠珠（CTX-OCT-Alg）中，采用差示扫描量热法（DSC）和傅里叶变换红外光谱（FTIR）研究药物相互作用，并用扫描电子显微镜（SEM）观察所形成的珠的形态。采用紫外分光光度法研究药物含量和释放情况。最后，评估了所有化合物的体外细胞毒性。结果表明，形成的 CTX-OCT 均匀偶联，粒径为 0.4mm。DSC 显示，由于聚合物相互作用较小，OCT 峰在 200°C 后出现延迟，从而使 OCT 峰发生位移。此外，FTIR 未显示出明显的相互作用。SEM 显示，空白 Ca-海藻酸钠珠中存在清晰的空腔，而 CTX-OCT-Alg 珠则显示出无空腔的填充珠。CTX-OCT-Alg 在 0.1N HCl 中几乎没有释放，而 CTX-OCT 在磷酸盐缓冲液 pH 7.4 中 300 分钟后完全释放。与游离药物相比，所有制剂均表现出良好的抗增殖活性。与游离药物相比，偶联 CTX-OCT-Alg 的制剂是通过 GIT 靶向治疗结直肠癌的有前途的平台。
