Fabrication of Drug-Loaded Torus-Shaped Alginate Microparticles and Kinetic Analysis of Their Drug Release.

We fabricated drug-loaded, microsized, and torus-shaped alginate microparticles (TSMs) by vortex-ring freezing (VRF), utilizing vortex ring formation and ionic cross-linking. The equivalent outer diameter of the TSMs was ca. 200 µm. Several model drugs, such as doxorubicin, heparin, lysozyme, and several dextran derivatives, have been successfully loaded into TSMs. Because the TSMs were fragile due to the limitation of the process conditions of the VRF, drug-loaded TSMs were subsequently cross-linked via "post-cross-linking" with CaCl2, SrCl2, or BaCl2 to increase the cross-linking density of the alginate matrix, thereby enhancing the stability of dextran (Dex)-loaded TSMs (Dex-TSMs) and enabling the sustained release of natural Dex of 10, 70, or 150 kDa and cationic or anionic Dex at a physiological pH. The release kinetics of Dexs showed molecular weight and charge dependence; a relatively dense network of the alginate matrix of post-cross-linked TSMs resulted in the sustained release of Dexs with high molecular weights, heparin, and lysozyme for up to 7 days in the release test. Furthermore, the solute diffusivities of the dextran derivatives in the bulk alginate matrix were measured by using fluorescence correlation spectroscopy, which supported the release kinetics of TSMs. Drug-loaded TSMs have potential as drug carriers for biopharmaceuticals, such as proteins.

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 micromolecular 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: KRASG12V). The AL/CDDP-nanogel/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.