Intraperitoneal Administration of a Cisplatin-Loaded Nanogel through a Hybrid System Containing an Alginic Acid-Based Nanogel and an In Situ Cross-Linkable Hydrogel for Peritoneal Dissemination of Ovarian Cancer

Intraperitoneal chemotherapy demonstrates potential applicability in the treatment of peritoneally disseminated ovarian cancer because the disseminated tumors can directly receive exposure to high concentrations of anticancer drugs. However, a considerable proportion of drugs, particularly micro-molecular and hydrophilic drugs, such as cisplatin (CDDP), are often excreted through glomerular filtration for a short period. To effectively deliver CDDP into peritoneally disseminated ovarian cancer tissues, we developed an alginate (AL)-based hybrid system in which a CDDP-loaded AL nanogel (AL/CDDP-nanogel) was encapsulated in an injectable AL-hydrogel cross-linked with calcium ions. This system enabled the sustained release of CDDP from the AL/CDDP-nanogel/AL-hydrogel hybrid for over a week. Herein, we constructed a peritoneally disseminated ovarian cancer mouse model using ovarian cancer cell lines with KRAS mutations (ID8-KRAS: KRAS(G12V)). The AL/CDDP-anogel/AL-hydrogel hybrid system showed significant antitumor activity in vivo. This therapy may be considered a novel strategy for the treatment of advanced-stage ovarian cancer with KRAS mutations.

Automated summary

The newly developed alginate-based hybrid system in intraperitoneal chemotherapy shows potential applicability for delivering cisplatin into peritoneally disseminated ovarian cancer tissues, allowing sustained drug release and significant antitumor activity in vivo. It may serve as a novel strategy for treating advanced-stage ovarian cancer with KRAS mutations.