Combined Thermosensitive Gel Co-Loaded with Dermaseptin-PP and PTX Liposomes for Effective Local Chemotherapy

Abstract

Ziyi Dong,* Qing Zhang,* Changhai Wang, Wenjun Hu, Xianglong Yu, Mingxue Guo, Xinyu Zhang, Meng Sun, Shouying Du, Yang Lu School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shouying Du, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email [email protected] Yang Lu, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email [email protected]: 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.Methods: 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.Results: 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.Conclusion: This study provided a promising nanomedicine platform for combining antimicrobial peptides and chemotherapeutic drugs for local chemotherapy.Keywords: cationic antimicrobial peptides, nanoparticles, temperature-sensitive, membrane-breaking, combination therapy

Keywords

• cationic antimicrobial peptides
• nanoparticles
• temperature-sensitive
• membrane-breaking
• combination therapy