title: RGD-modified pH-sensitive liposomes for docetaxel tumor targeting.
abstract: Phosphatidylethanolamine-based pH-sensitive liposomes of various compositions have been described as efficient systems for delivery of therapeutic molecules into tumor cells. The aim of this work was to develop a drug delivery system based on pH-sensitive liposomes (PLPs) that were modified with arginine-glycine-aspartic acid (RGD) peptide to enhance the effectiveness of docetaxel treatment. Docetaxel/coumarin-6 loaded PLPs were prepared by the thin-film dispersion method and characterized in detail, including by particle size, polydispersity, zeta potential and drug encapsulation efficiency. In vitro studies using MCF-7, HepG2and A549 cells were employed to investigate cytotoxicity and cellular uptake of the drug solution or docetaxel/coumarin-6 loaded PLPs. The accumulation of 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled liposomes in vivo was studied through tumor section imaging of xenograft mouse models of MCF-7 24h after intravenous administration. The particle size of the non-coated or RGD modified PLPs ranged between 146 and 129nm. Drug release in vitro was modestly prolonged and had good pH sensitivity. In the in vitro study, RGD-coated PLPs showed higher cytotoxicity and cellular uptake relative to non-coated ones. The results of the in vivo study showed that RGD-coated PLPs had higher fluorescence, which suggested a more efficient accumulation than normal PLPs in tumors. In conclusion, these results confirmed RGD-modified PLPs as a potential drug delivery system to achieve controlled release and tumor targeting.
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Minglu
authors: M
authors: Chang
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China; Department of Pharmacy, Anhui Provincial Hospital, Hefei 230001, China.
authors: Shanshan
authors: S
authors: Lu
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Fang
authors: F
authors: Zhang
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Tiantian
authors: T
authors: Zuo
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Yuanyuan
authors: Y
authors: Guan
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Ting
authors: T
authors: Wei
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China.
authors: Wei
authors: W
authors: Shao
authors: School of Pharmaceutical Science, Shandong University, Jinan 250012, China. Electronic address: syb0115@163.com.
authors: Guimei
authors: G
authors: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009842:Oligopeptides; D043823:Taxoids; D000077143:Docetaxel; C047981:arginyl-glycyl-aspartic acid
keywords: Docetaxel; Drug delivery; RGD peptide; Tumor targeting; pH-sensitive liposomes