Doxorubicin·Hydrochloride/Cisplatin-Loaded Hydrogel/Nanosized (2-Hydroxypropyl)-Beta-Cyclodextrin Local Drug-Delivery System for Osteosarcoma Treatment In Vivo

Abstract

Osteosarcoma (OSA) is a difficult cancer to treat due to its tendency for relapse and metastasis; advanced methods are therefore required for OSA treatment. In this study, we prepared a local drug-delivery system for OSA treatment based on doxorubicin·hydrochloride (DOX·HCl)/cisplatin (CP)-loaded visible light-cured glycol chitosan (GC) hydrogel/(2-hydroxypropyl)-beta-cyclodextrin (GDHCP), and compared its therapeutic efficiency with that of DOX·HCl-and CP-loaded GC hydrogels (GD and GHCP). Because of diffusion driven by concentration gradients in the swollen matrix, the three hydrogels showed sustained releases of DOX·HCl and CP over 7 days, along with initial 3-h bursts. Results of in vitro cell viability and in vivo animal testing revealed that GDHCP had a stronger anticancer effect than GD and GHCP even though there were no significant differences. Body weight measurement and histological evaluations demonstrated that the drug-loaded GC hydrogels had biocompatibility without cardiotoxicity or nephrotoxicity. These results suggested that GDHCP could be a good platform as a local drug-delivery system for clinical use in OSA treatment.

Injectable Glycol Chitosan Hydrogel Containing Folic Acid-Functionalized Cyclodextrin-Paclitaxel Complex for Breast Cancer Therapy

“…Our previous study proved that the visible light-cured MGC hydrogel not only made it easy to load the anti-cancer drugs in the hydrogel precursor solution before photocuring but also showed a sustained release behavior by drug diffusion from the bulk to the surface of the hydrogel, resulting from the structural properties of the hydrogel after photocuring [ 2 , 3 , 4 , 5 ]. The release behavior of PTX in MGC/PTX, MGC/CD-ic-PTX, and MGC/CDPF-ic-PTX at 37 °C for 3 days using PBS (pH 7.4) was investigated ( Figure 5 ).…”

“…MGC was prepared according to our previous studies [ 2 , 3 , 4 , 5 , 17 ]. Glycidyl methacrylate (GM; 0.05 mmol, 7 mg) was added to an aqueous GC solution (0.003 mmol, 1.5 g; 500 mL), followed by adjustment to pH 9.…”

“…Local drug delivery systems, which are intratumorally implanted and adjacent to cancer tissues, are suitable for effective cancer treatment because they can achieve high therapeutic capacity resulting from the high concentration of anti-cancer drugs around cancer tissues, followed by minimizing normal tissue toxicity and improving low bioavailability [ 1 , 2 , 3 , 4 , 5 ]. Therefore, to date, several kinds of platforms, such as films for releasing drugs, gels, wafers, rods, and particles, have been designed for localized drug delivery systems [ 1 ].…”

“…Among these platforms, hydrogels have attracted much attention because of their injectability, along with ease of drug targeting to cancer tissue and minimal toxicity to normal tissues [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Furthermore, these injectable hydrogels improve the water solubility of anti-cancer drugs, thereby decreasing the required number of drugs and increasing the amount that reaches the targeted sites [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. These characteristics are closely related to the improvement in targeted drug delivery.…”

Eggshell Membrane/Gellan Gum Composite Hydrogels with Increased Degradability, Biocompatibility, and Anti-Swelling Properties for Effective Regeneration of Retinal Pigment Epithelium

“…Among hydrogel drug delivery systems, injectable hydrogels have earned a reputation as attractive matrices for delivering drugs in a controlled and targeted manner [ 14 ]. Hydrogels can promote cell migration, as their matrix can be penetrated with water molecules and swollen, and then cells are released to the target site [ 15 , 16 , 17 ]. RPE cell transplantation using a hydrogel as a carrier offers an accessible alternative to retinal regeneration, taking into account that scaffold-based transplantation is more effective in obtaining living cells than the alternative suspension method [ 18 ].…”