Oxaliplatin-loaded chemically cross-linked hydrogels for prevention of postoperative abdominal adhesion and colorectal cancer therapy

• Published in: International journal of pharmaceutics Vol. 565; pp. 50 - 58
• Main Authors: Lee, Jee Eun, Abuzar, Sharif Md, Seo, Yeji, Han, Hyeji, Jeon, Youngbae, Park, Eun Jung, Baik, Seung Hyuk, Hwang, Sung-Joo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.06.2019
• Subjects: Carboxymethyl cellulose sodium; Colorectal cancer; Hyaluronic acid; Hydrogel; Intra-abdominal anti-adhesion barrier; Oxaliplatin; Colorectal cancer; Hyaluronic acid (PubChem CID: 24847767); Adipic acid dihydrazide (PubChem CID: 66117); Intra-abdominal anti-adhesion barrier; Carboxymethyl cellulose sodium (PubChem CID: 23706213); Hyaluronidase (CAS Number 91820602); Oxaliplatin; CRC; 1-Ethyl-3-(3-(dimethylaminopropyl)carbodi-imide (PubChem CID: 15908); CMCNa; Carboxymethyl cellulose sodium; HA; Hydrogel; Hyaluronic acid
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.04.065

[Display omitted] Colorectal cancer (CRC) is the third most commonly diagnosed cancer among both men and women worldwide. New therapeutic strategies involving cytoreductive surgery and intra-peritoneal chemotherapy could lead to a definitive cure in some cases. However, postoperative intra-abdominal adhesion can cause further complications. In this study, hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based novel cross-linked hydrogels (HC hydrogels) were synthesized and fully characterized. We demonstrated that varied compositions of HA and CMCNa altered the microstructure, rheology, and degradation behavior of hydrogels. Pre-constructed hydrogels were further loaded with oxaliplatin to prevent intra-abdominal adhesion following chemotherapy. Sustained release of oxaliplatin was observed from hydrogels compared that from solutions, which release drugs through diffusion, following the Higuchi and Korsmeyer-Peppas models. Moreover, low adhesion scores in an in vivo SD rat model demonstrated inhibition of intra-peritoneal adhesion in response to HC hydrogels. Therefore, HC hydrogels offer a novel formulation strategy for providing an intra-abdominal anti-adhesion barrier after cytoreductive surgery and intra-peritoneal chemotherapy for CRC treatment.