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

Sun Jung Yoon,Young Jae Moon,Heung Jae Chun,Dae Hyeok Yang

doi:10.3390/nano9121652

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.

Highlights

Osteosarcoma (OSA) is a common primary bone cancer that frequently occurs in young people with bimodal peak incidence [1]
OSA is generally treated with anticancer drugs for approximately 10 weeks before surgery; this treatment is known as neoadjuvant chemotherapy
These findings demonstrated that the glycol chitosan (GC) hydrogel can be used as a local drug-delivery system for anticancer drugs to targeted sites

Summary

Introduction

Osteosarcoma (OSA) is a common primary bone cancer that frequently occurs in young people with bimodal peak incidence [1]. Anticancer drugs for chemotherapy include doxorubicin (DOX), cisplatin (CP), epirubicin, ifosfamide, cyclophosphamide, eotposide, gemcitabine, and topotecan. These anticancer drugs improve the survival duration of patients with OSA; the cancer is still prone to relapse and metastasis. Among drug-carrier systems, nanomaterial-based systemic drug carriers require several characteristics to deliver anticancer drugs to targeted sites [9]. These characteristics include shape, size and surface charge, which improve passive targeting, and ligand conjugation, which improves active targeting [9]. In vitro and in vivo anticancer effects were evaluated using a KHOS/NP human OSA cell line and an OSA cancer-bearing xenograft mouse model, respectively

Materials

In Vitro Cell Viability

In Vivo

Histological Evaluations

Findings

Conclusions