Evaluation of synthetic/reconstituted high-density lipoproteins as delivery vehicles for paclitaxel.
Reconstituted (synthetic) high-density lipoprotein particles carrying paclitaxel (rHDL/PTX) were prepared with substantially higher PTX content than reported earlier. The rHDL/PTX complexes seemed to be primarily spherical nanoparticles when examined via electron microscopy, with a constant composition, molecular weight and exceptional stability even after ultracentrifugation and storage for up to 6 months. The rHDL/PTX nanoparticles had superior cytotoxicity against several cancer cell lines (MCF7, DU145, OV1063 and OVCAR-3), the half maximal inhibitory concentration (IC50) having been found to be 5-20 times lower than that of the free drug. Studies with mice showed that the rHDL/PTX nanoparticles were substantially better tolerated than the corresponding dosages of either Taxol or Abraxane.
McConathy
Walter J
WJ
Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
Nair
Maya P
MP
Paranjape
Sulabha
S
Mooberry
Linda
L
Lacko
Andras G
AG
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D002788:Cholesterol Esters / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D008075:Lipoproteins, HDL / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines / Q000737:chemistry; D015431:Weight Loss / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines; C014409:cholesteryl oleate; D002784:Cholesterol; D017239:Paclitaxel