title: Co-delivery of docetaxel and palmitoyl ascorbate by liposome for enhanced synergistic antitumor efficacy.
abstract: Palmitoyl ascorbate (PA) as an antioxidant has the potential for the treatment of cancer. In the present study, a nanocarrier system was developed for co-delivery of docetaxel (DOC) with palmitoyl ascorbate and the therapeutic efficacy of a combination drug regimen was investigated. For this purpose, different ratios of docetaxel and palmitoyl ascorbate were co-encapsulated in a liposome and they all showed high encapsulation efficiency. The average diameters of the liposomes ranged from 140 to 170 nm. Negative zeta potential values were observed for all systems, ranged from -40 mV to -56 mV. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released slowly. Moreover, the liposome loading drugs with DOC/PA concentration ratio of 1:200 showed the highest anti-tumor activity to three different types of tumor cells. The higher in vivo therapeutic efficacy with lower systemic toxicity of the DOC-PA200-LPs was also verified by the H22 tumor bearing mice model. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against hepatic carcinoma.
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Junxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Chaorui
authors.initials: C
authors.lastname: Guo
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Ali
authors.initials: A
authors.lastname: Fan
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, #639 Longmain Avenue, Jiangning District, Najing, 211198, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004339:Drug Compounding; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008813:Mice, Inbred ICR; D053769:Nanocapsules; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D043823:Taxoids / Q000008:administration & dosage* / Q000633:toxicity; D047368:Tumor Burden
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D008081:Liposomes; D053769:Nanocapsules; D014677:Pharmaceutical Vehicles; D043823:Taxoids; D000077143:Docetaxel; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid