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3D-printed chitosan-pectin-sodium alginate scaffolds for post-surgical peritoneal wound dressing and sustained delivery of oxaliplatin

  • Linh Dinh,
  • Rukesh Machamasi,
  • Chae Jeong Kim,
  • Jong-Ju Lee,
  • Yeonju Choi,
  • Haneul Kim,
  • Lanesa Mahon,
  • Ayla Grabenbauer,
  • Bingfang Yan,
  • Sung-Joo Hwang

摘要

Purpose

Hydrogel films have been extensively studied for controlled drug delivery for cancer treatment. Moreover, hydrogels are widely used for wound-healing effects and to prevent adhesions after tumor-removal operations. Despite ongoing developments in postoperative wound dressing agents, adhesion remains a significant challenge in clinical practice. Particularly in advanced colorectal cancer patients, intraperitoneal adhesion coupled with reoccurrence of peritoneal carcinomatosis remains a disease progression with an extremely low survival rate. Thus, local application of postoperative chemotherapy-loaded hydrogels could be an optimal treatment strategy for the cases. Additionally, depending on the patient, the target tumor site, and the wound, an ideal wound dressing can carry an accurate, specific dose of oxaliplatin. Therefore, 3D-printed gel scaffolds can be a prime example of customized drug delivery systems.

Methods

In this current study, several chitosan-pectin-sodium alginate systems were prepared, and their rheological performances were characterized. The statistical design of experiments was applied to develop the 3D-printed hydrogel scaffolds. Cell viability assays were performed to assess the cytotoxicity of the hydrogels. We demonstrated the feasibility and printability of C2P1NaA incorporating oxaliplatin as a potential postoperative treatment. The release profiles of oxaliplatin from the hydrogels were investigated.

Results

C2P1NaA was chosen as the optimal gel. In vitro dissolution tests demonstrated sustained oxaliplatin release for over 2 weeks. However, “burst release” and reverse degradation curves of oxaliplatin were observed. Additionally, the C2P1NaA hydrogels and 3D-printed gels were evaluated for in vivo anti-adhesion barrier and wound healing efficiency in Sprague-Dawley rats.