Gemcitabine and γ-cyclodextrin/docetaxel inclusion complex-loaded liposome for highly effective combinational therapy of osteosarcoma

The aim of the present investigation was to formulate a docetaxel (DTX) and gemcitabine (GEM) co-loaded PEGylated liposome (DTX/GEM-L) to increase the therapeutic efficacy in osteosarcoma (OS). 2-Hydroxypropyl-γ-cyclodextrin/DTX inclusion complex was made to increase DTX aqueous solubility. DTX/GEM-L was characterized for morphological shape and size parameters. Release study showed a sustained release pattern for both the drugs. The nanocarriers based combinational drug significantly increased the cytotoxic effect than the free drug combination at the same concentration. The cell cycle analysis showed a predominant G2/M phase arrest for combinational drug. Importantly, more than 20% of cells were in late apoptosis chamber for DTX/GEM-L treatment with significant proportion of cells in the early apoptosis and necrotic phases. The antitumor efficacy was tested in MG63 cancer cell bearing xenograft nude mice. Results showed that DTX/GEM-L significantly reduced the tumor burden comparing to that of free combination cocktail. The PEGylated liposome successfully delivered the anticancer drugs in the osteosarcoma tumor interstitial spaces via EPR effect. DTX/GEM-L showed excellent safety profile along with the remarkable tumor suppression ability. Overall, results suggest that nanocarriers-based delivery system remarkably enhanced the apoptosis and cytotoxicity and increased the potency of combinational drug regimen.

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