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

Abstract

Introduction 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.

Stimulus‐responsive nano lipidosome for enhancing the anti‐tumour effect of a novel peptide Dermaseptin‐PP

“…Dermaseptin‐PP liposomes were prepared according to the method of Ziyi Dong et al. [7]: Dermaseptin‐PP liposomes were prepared by membrane hydration. SPC, CHO, and DSPE‐Hyd‐PEG 2k (Figure 1) were weighed at a molar ratio of 65:25:10 (mol:mol:mol) and then mixed and dissolved in an appropriate amount of methylene chloride.…”

“…Some antimicrobial peptides with α helix structure often show excellent anticancer activity, so they are also called Anticancer peptides (ACPs) [5,6]. Dermaseptins (DRSs) are a family of peptides that are part of the skin secretions of several Hylid frogs, particularly from the Agalychnis and Phyllomedusa families [7]. DRSs are classified as Antimicrobial peptides (AMPs) because they show efficacy in vitro against some Grampositive and Gram-negative bacteria, parasites, yeast, protozoa, and viruses and show immunomodulation effects [8].…”

“…DRSs have multiple anti-tumour mechanisms [8,10,11], which can induce necrosis through cell membrane lysis, initiate apoptosis through mitochondrial membrane rupture, and some other non-lytic membrane action modes [12,13]. At the same time, DRSs can also enhance the efficacy of chemotherapy drugs and improve their sense of them [7]. In addition, DRSs themselves have specific tumour selectivity and less damage to normal tissues and cells [14].…”