title: Gemcitabine and γ-cyclodextrin/docetaxel inclusion complex-loaded liposome for highly effective combinational therapy of osteosarcoma.
abstract: 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.
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Orthopaedic, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Qing-Hu
authors.initials: QH
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China. Electronic address: liuping21@hotmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D000077143:Docetaxel; D004338:Drug Combinations; D065546:Drug Liberation; D006801:Humans; D008081:Liposomes; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D047408:gamma-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D008081:Liposomes; D043823:Taxoids; D047408:gamma-Cyclodextrins; D003841:Deoxycytidine; D000077143:Docetaxel; D020169:Caspases; C023792:gamma-cyclodextrin; D000093542:Gemcitabine
keywords: Cyclodextrin; Docetaxel; Gemcitabine; Liposome; Osteosarcoma