Doxorubicin and CD‑CUR inclusion complex co‑loaded in thermosensitive hydrogel PLGA‑PEG‑PLGA localized administration for osteosarcoma

Yang,Zhiming; Liu,Jianguo; Lu,Yichen

doi:10.3892/ijo.2020.5067

Doxorubicin and CD‑CUR inclusion complex co‑loaded in thermosensitive hydrogel PLGA‑PEG‑PLGA localized administration for osteosarcoma

Authors:
- Zhiming Yang
- Jianguo Liu
- Yichen Lu
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Affiliations: Department of Thoracic Surgery, Anhui Provincial Cancer Hospital (The First Affiliated Hospital of University of Science and Technology of China West District), Hefei, Anhui 230000, P.R. China, Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Oncology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410002, P.R. China
Published online on: May 19, 2020 https://doi.org/10.3892/ijo.2020.5067
Pages: 433-444
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Combination therapy is a promising and prevalent strategy for osteosarcoma treatment. Curcumin (CUR), as a chemosensitizer, improves the antitumor effect of first‑line chemotherapy drugs. However, due to its poor solubility and instability in physiological conditions, the bioavailability of CUR is limited. In order to improve the physicochemical properties of natural CUR, β‑cyclodextrin was adopted to generate a β‑cyclodextrin curcumin (CD‑CUR) inclusion complex. A thermosensitive hydrogel, poly(D,L‑lactide‑co‑glycolide)-poly(ethylene‑glycol)‑poly(D,L‑lactide‑co‑glycolide), was selected and synthesized to co‑deliver doxorubicin (DOX) and CD‑CUR to tumor sites. The dual‑drug delivery system (gel+DOX+CD‑CUR) was prepared by mixing drugs with hydrogels and had a perfect sol‑gel phase transition temperature (18.3˚C for 20% concentration). Both DOX and CUR were released from hydrogels in a sustained manner in PBS (pH 7.4) medium. The combination therapy based on DOX+CD‑CUR exhibited higher antitumor activity than monotherapies in vitro. Combined CD‑CUR therapy significantly downregulated Bcl‑2 expression and upregulated caspase‑3 expression, suggesting that DOX combined with CD‑CUR treatment has a higher apoptosis‑inducing efficiency. The antitumor efficiency of the gel+DOX+CD‑CUR strategy was evaluated in K‑7 tumor‑bearing mice, and this localized combination therapy demonstrated a higher antitumor efficiency compared with free DOX+CD‑CUR or single‑drug strategies. There were no significant differences in body weight and histological changes of major organs in each group. Therefore, the present combination treatment based on hydrogel may be a feasible approach to co‑deliver DOX and CD‑CUR to osteosarcoma tumor sites in clinical practice.

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