title: Self-assembled biodegradable nanoparticles developed by direct dialysis for the delivery of paclitaxel.
abstract: OBJECTIVE
  The main objective of this study was to obtain self-assembled biodegradable nanoparticles by a direct dialysis method for the delivery of anticancer drug. The in vitro cellular particle uptake and cytotoxicity to C6 glioma cell line were investigated.
  
  
  METHODS
  Self-assembled anticancer drugs--paclitaxel-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLA) nanoparticles--were achieved by direct dialysis. The physical and chemical properties of nanoparticles were characterized by various state-of-the-art techniques. The encapsulation efficiency and in vitro release profile were measured by high-performance liquid chromatography. Particle cellular uptake was studied using confocal microscopy, microplate reader, and flow cytometry. In addition, the cytotoxicity of this drug delivery system was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C6 glioma cell line to predict the possible dose response of paclitaxel-loaded PLGA and PLA nanoparticles.
  
  
  RESULTS
  PLGA and PLA nanoparticles with or without vitamin E tocopherol polyethylene glycol succinate (TPGS) as an additive were obtained, in which the sustained release of paclitaxel of more than 20 days was achieved. The coumarin6-loaded PLGA and PLA nanoparticles could penetrate the C6 glioma cell membrane and be internalized. The cytotoxicity of paclitaxel-loaded nanoparticles seemed to be higher than that of commercial Taxol after 3 days incubation when paclitaxel concentrations were 10 and 20 microg/ml.
  
  
  CONCLUSIONS
  Direct dialysis could be employed to achieve paclitaxel-loaded PLGA and PLA nanoparticles, which could be internalized by C6 glioma cells and enhance the cytotoxicity of paclitaxel because of its penetration to the cytoplasm and sustained release property.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Xie
authors.forename: Chi-Hwa
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001932:Brain Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003956:Dialysis; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004563:Electrochemistry; D005079:Excipients; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007267:Injections; D007275:Injections, Intravenous; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D017239:Paclitaxel