title: Novel pH-sensitive polysialic acid based polymeric micelles for triggered intracellular release of hydrophobic drug.
abstract: Polysialic acid (PSA), a non-immunogenic and biodegradable natural polymer, is prone to hydrolysis under endo-lysosomal pH conditions. Here, we synthesized an intracellular pH-sensitive polysialic acid-ursolic acid conjugate by a condensation reaction. To further test the drug loading capability, we prepared paclitaxel-loaded polysialic acid-based amphiphilic copolymer micelle (PTX-loaded-PSAU) by a nanoprecipitation method. Results showed PTX-loaded-PSAU exhibited well-defined spherical shape and homogeneous distribution. The drug-loading was 4.5% with an entrapment efficiency of 67.5%. PTX released from PTX-loaded-PSAU was 15% and 42% in 72 h under simulated physiological condition (pH 7.4) and mild acidic conditions (pH 5.0), respectively. In addition, In vitro cytotoxicity assay showed that PTX-loaded-PSAU retained anti-tumor (SGC-7901) activity with a cell viability of 53.8% following 72 h incubation, indicating PTX-loaded-PSAU could efficiently release PTX into the tumor cells. These results indicated that the pH-responsive biodegradable PTX-loaded-PSAU possess superior extracellular stability and intracellular drug release ability.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Wuxia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Dong
authors.affiliation: College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Mu
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Niu
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: jduan@nwsuaf.edu.cn.
authors.forename: Jinyou
authors.initials: J
authors.lastname: Duan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D012794:Sialic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D017239:Paclitaxel; D012794:Sialic Acids; D014315:Triterpenes; D000097245:Ursolic Acid; C021319:polysialic acid
keywords: Paclitaxel; Polymeric micelles; Polysialic acid; pH-sensitive