1 research outputs found
Localized Co-delivery of Doxorubicin, Cisplatin, and Methotrexate by Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment
Localized
cancer treatments with combination drugs have recently emerged as
crucial approaches for effective inhibition of tumor growth and reoccurrence.
In this study, we present a new strategy for the osteosarcoma treatment
by localized co-delivery of multiple drugs, including doxorubicin
(DOX), cisplatin (CDDP) and methotraxate (MTX), using thermosensitive
PLGA–PEG–PLGA hydrogels. The release profiles of the
drugs from the hydrogels were investigated in vitro. It was found
that the multidrug coloaded hydrogels exhibited synergistic effects
on cytotoxicity against osteosarcoma Saos-2 and MG-63 cells in vitro.
After a single peritumoral injection of the drug-loaded hydrogels
into nude mice bearing human osteosarcoma Saos-2 xenografts, the hydrogels
coloaded with DOX, CDDP, and MTX displayed the highest tumor suppression
efficacy in vivo for up to 16 days, as well as led to enhanced tumor
apoptosis and increased regulation of the expressions of apoptosis-related
genes. Moreover, the monitoring on the mice body change and the ex
vivo histological analysis of the key organs indicated that the localized
treatments caused less systemic toxicity and no obvious damage to
the normal organs. Therefore, the approach of localized co-delivery
of DOX, CDDP, and MTX by the thermosensitive hydrogels may be a promising
approach for enhanced osteosarcoma treatment