School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People's Republic of China.
Int J Nanomedicine. 2023 Jan 21;18:413-424. doi: 10.2147/IJN.S385470. eCollection 2023.
Chemotherapeutic drugs are often ineffective due to the delivery. Local chemotherapy, which has high drug concentration, low systemic toxicity, and long duration, has shown excellent potential. Cationic antimicrobial peptides have been proved to enhance the tumor cells' uptake of chemotherapeutic drugs through the membrane-breaking effect. In this study, we designed and developed a thermosensitive gel co-loaded with Dermaseptin-PP and paclitaxel liposomes to increase local chemotherapy.
The paclitaxel liposomes were prepared. Then, it was co-loaded with Dermaseptin-PP in a poloxamer-based thermosensitive gel to obtain Dermaseptin-PP/paclitaxel liposomes gel. The thermosensitivity of gels was investigated by test tube inversion method. The rheology was tested by rheometer. The in vitro cytotoxicity and the permeation in tumor of gels were examined by H157 cells and the 3D cell model, respectively. The retention in tumor and antitumor activity of gels were evaluated by H157 tumor-bearing nude mice.
The particle size of paclitaxel liposomes was 148.97 ± 0.21 nm. The encapsulation rate was 86.1%, and the drug loading capacity was 19.4%. The gels had slow-release and temperature-sensitive properties. The porous 3D network structure of the gels could ensure that the drug was fixed into the tumor. In vitro and in vivo distribution studies showed that Dermaseptin-PP promoted the permeation of the gels in H157 multicellular tumor spheres and achieved longer retention in tumor. In vitro and in vivo antitumor studies demonstrated that Dermaseptin-PP/paclitaxel liposomes gel significantly inhibited the growth of tumors for local chemotherapy with good biosafety.
This study provided a promising nanomedicine platform for combining antimicrobial peptides and chemotherapeutic drugs for local chemotherapy.
由于药物递送的问题，化疗药物往往效果不佳。局部化疗具有药物浓度高、全身毒性低、作用时间长等优点，显示出了巨大的潜力。阳离子抗菌肽已被证明通过破坏细胞膜的作用增强了肿瘤细胞对化疗药物的摄取。在本研究中，我们设计并开发了一种共载 Dermaseptin-PP 和紫杉醇脂质体的温敏凝胶，以增强局部化疗。
制备紫杉醇脂质体。然后，将其与 Dermaseptin-PP 共载于泊洛沙姆基温敏凝胶中，得到 Dermaseptin-PP/紫杉醇脂质体凝胶。通过试管倒置法考察凝胶的温敏性。采用流变仪考察流变学性能。分别采用 H157 细胞和三维细胞模型考察凝胶的体外细胞毒性和肿瘤渗透性能。采用 H157 荷瘤裸鼠评价凝胶的肿瘤滞留和抗肿瘤活性。
紫杉醇脂质体的粒径为 148.97±0.21nm，包封率为 86.1%，载药量为 19.4%。凝胶具有缓慢释放和温度敏感性。凝胶的多孔 3D 网络结构可以确保药物固定在肿瘤中。体外和体内分布研究表明，Dermaseptin-PP 促进了凝胶在 H157 多细胞肿瘤球体中的渗透，实现了更长时间的肿瘤滞留。体外和体内抗肿瘤研究表明，Dermaseptin-PP/紫杉醇脂质体凝胶显著抑制了肿瘤生长，实现了局部化疗的良好生物安全性。
本研究为抗菌肽与化疗药物联合用于局部化疗提供了一种有前途的纳米医学平台。
