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A novel thermosensitive poloxamer-hyaluronic acid- kappa-carrageenan-based hydrogel anti-adhesive agent loaded with 5-fluorouracil: A preclinical study in Sprague-Dawley rats

Authors
 Linh Dinh  ;  Jiyeon Hong  ;  Dong Min Kim  ;  Gawon Lee  ;  Eun Jung Park  ;  Seung Hyuk Baik  ;  Sung-Joo Hwang 
Citation
 INTERNATIONAL JOURNAL OF PHARMACEUTICS, Vol.621 : 121771, 2022-06 
Journal Title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN
 0378-5173 
Issue Date
2022-06
MeSH
Animals ; Carrageenan ; Fluorouracil ; Hyaluronic Acid ; Hydrogels* ; Poloxamer* ; Rats ; Rats, Sprague-Dawley ; Temperature ; Tissue Adhesions / drug therapy ; Tissue Adhesions / prevention & control
Keywords
Colorectal cancer ; Hyaluronic acid ; Hydrogel ; Kappa-carrageenan ; Peritoneal anti-adhesion barrier ; Poloxamer 407
Abstract
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S037851732200326X?via%3Dihub
DOI
10.1016/j.ijpharm.2022.121771
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Eun Jung(박은정) ORCID logo https://orcid.org/0000-0002-4559-2690
Baik, Seung Hyuk(백승혁) ORCID logo https://orcid.org/0000-0003-4183-2332
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188681
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