Locally Controlled Release of Methotrexate and Alendronate by Thermo-Sensitive Hydrogels for Synergistic Inhibition of Osteosarcoma Progression

Hongli Shan; Ke Li; Duoyi Zhao; Changliang Chi; Qinyuan Tan; Xiaoqing Wang; Jinhai Yu; Meihua Piao

doi:10.3389/fphar.2020.00573

Locally Controlled Release of Methotrexate and Alendronate by Thermo-Sensitive Hydrogels for Synergistic Inhibition of Osteosarcoma Progression

Front Pharmacol. 2020 May 19:11:573. doi: 10.3389/fphar.2020.00573. eCollection 2020.

Authors

Hongli Shan¹, Ke Li², Duoyi Zhao², Changliang Chi³, Qinyuan Tan³, Xiaoqing Wang³, Jinhai Yu⁴, Meihua Piao⁵

Affiliations

¹ Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, China.
² Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, Shenyang, China.
³ Department of Urology, the First Hospital of Jilin University, Changchun, China.
⁴ Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China.
⁵ Department of Anesthesiology, The First Hospital of Jilin University, Changchun, China.

Abstract

Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG₄₅-PLV₁₉) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG₄₅-PLV₁₉ shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.

Keywords: controlled drug release; local injection; osteosarcoma; synergistic chemotherapy; thermo-sensitive hydrogel.