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Injectable rhein-assisted crosslinked hydrogel for efficient local osteosarcoma chemotherapy.
Lei Zhang1, Ying-Xuan Liu2, Ya-Ting Yao2
1Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
International Journal of Pharmaceutics
|January 26, 2023
Summary
This study introduces a novel hydrogel combining rhein and doxorubicin for osteosarcoma treatment. The new formulation enhances drug efficacy while reducing toxicity, offering a promising single-dose therapy for bone cancer.
Area of Science:
- Biomaterials Science
- Oncology
- Drug Delivery Systems
Background:
- Osteosarcoma (OS) is a primary bone cancer predominantly affecting children and adolescents.
- Current treatments using doxorubicin hydrochloride (DOX) are limited by drug resistance and severe side effects from high doses.
- There is a critical need for more effective and less toxic therapeutic strategies for OS.
Purpose of the Study:
- To develop an injectable, crosslinked hydrogel system (PVA@RH@DOX hydrogel, PRDH) for efficient osteosarcoma treatment.
- To evaluate the combined therapeutic effects of rhein (RH) and DOX within the hydrogel formulation.
- To assess the potential of PRDH as a low-toxicity, long-term, single-administration treatment for OS.
Main Methods:
- Preparation of PRDH by loading DOX and RH into a polyvinyl alcohol (PVA) solution.
- Cytotoxicity assays and live/dead staining to evaluate OS cell killing efficiency.
- Wound healing and Transwell assays to assess the inhibition of OS cell metastasis and invasion.
- In vivo evaluation of long-lasting antitumor effects and hydrogel formation properties.
Main Results:
- The combination of RH and DOX within the hydrogel demonstrated superior efficacy in killing OS cells compared to DOX alone, even at lower concentrations.
- PRDH significantly inhibited the migration, invasion, and metastasis of OS cells.
- A single dose of PRDH provided a sustained antitumor effect, effectively suppressing tumor proliferation and metastasis.
- Rhein (RH) actively facilitated the crosslinking and formation of the PVA-based hydrogel.
Conclusions:
- The developed PRDH system offers an effective and low-toxicity therapeutic approach for osteosarcoma.
- This injectable hydrogel enables a single administration for long-term treatment, overcoming limitations of conventional DOX therapy.
- The findings present PRDH as a promising alternative for clinical osteosarcoma treatment, broadening therapeutic options.
