Biocompatibility and Drug Release Properties of Carboxymethyl Cellulose Hydrogel for Carboplatin Delivery

TL;DR

A new hydrogel made from carboxymethyl cellulose was developed to safely and effectively deliver the cancer drug carboplatin over time.

Contribution

A novel ECH-crosslinked CMC hydrogel was developed for controlled carboplatin delivery with demonstrated biocompatibility and sustained release.

Findings

CMCG showed pH-dependent swelling and released ~70% of CBP within 12 hours in PBS.

CBP-CMCG was non-cytotoxic to normal cells but showed sustained antitumor effects in cancer cells.

The hydrogel platform enables prolonged therapeutic activity of CBP compared to free drug.

Abstract

Carboxymethylcellulose (CMC) is a biocompatible and biodegradable polysaccharide suitable for biomedical applications. Herein, an epichlorohydrin (ECH)-crosslinked CMC hydrogel (CMCG) was developed as a carrier for sustained drug release. Ether-type crosslinking between the hydroxyl groups of CMC and ECH yielded a transparent, highly water-absorbent gel. Structural analyses employing Fourier-transform infrared and solid-state 13C nuclear magnetic resonance spectroscopies confirmed successful crosslinking, and the hydrogel exhibited pH-dependent swelling. Carboplatin (CBP), a platinum-based anticancer drug, was incorporated into CMCG to prepare CBP-CMCG. In phosphate-buffered saline (pH 7.4), approximately 70% of CBP was released within 12 h, followed by a plateau phase, indicating diffusion-controlled release. Cytocompatibility assays using WI-38 normal human fibroblasts demonstrated that CMCG was non-cytotoxic, whereas free CBP induced significant cell death. In colorectal cancer HT-29 cells, CBP-CMCG exhibited gradual cytotoxicity, resulting in >80% nonviable cells after 24 h, indicating a sustained antitumor effect compared with free CBP. These results demonstrate that the newly developed ECH-crosslinked CMC hydrogel is a safe and effective platform for controlled drug delivery, enabling sustained release and prolonged therapeutic activity of CBP.

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