Although the first-choice treatment for colorectal cancer is cytoreductive surgery combined with chemotherapy, post-surgical peritoneal adhesion and extant malignancy can cause fatal complications. Studies examining hydrogel-based postoperative anti-adhesion treatments are still limited. In this study, several formulations of 5-fluorouracil (5-FU) loaded into hyaluronic acid (HA) and kappa-carrageenan (kCGN)-poloxamer 407 (P407)-based cross-linked hydrogels were prepared and evaluated in vitro and in vivo for their efficacy in preventing adhesion. These hydrogels met a set of desired specifications such as thermosensitive behavior, strong elasticity at body temperature (tan δ < 1.0 at 37 °C), and ability to encapsulate hydrophilic drug and deliver it in a sustained released manner. Our secondary purpose is to provide in situ 5-FU for additional local antitumor effect when the anti-adhesion agent is spread over the tumor site. Over 60% of the total loaded drug was released within 4 h, and about 80% of 5-FU was released after three days. Both the Higuchi and Korsmeyer-Peppas models showed that the mechanism of sustained drug release involved diffusion. The constructed hydrogels were evaluated for in vivo intra-abdominal anti-adhesion barrier efficiency; the HA/kCGN 1%/3% w/v hydrogel formulation showed the best anti-adhesion effect in this preclinical study using Sprague-Dawley rat models.
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 2022 Jun 10|
Bibliographical noteFunding Information:
We thank the Yonsei Center for Research Facilities (YCRF, Seoul, Republic of Korea) and Anton Paar Korea Ltd. (Seoul, Republic of Korea) for the providing analytical support. Thanks go to Editage (www.editage.co.kr) for English language editing.
This work was supported by the Mid-Career Researcher Program (No. NRF-2021R1A2C2008834) and Basic Research Infrastructure Support Program (University-Centered Labs-2018R1A6A1A03023718) through the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT).
© 2022 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science