title: Development and evaluation of a novel TPGS-mediated paclitaxel-loaded PLGA-mPEG nanoparticle for the treatment of ovarian cancer.
abstract: One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.
authors.affiliation: Tongde Hospital of Zhejiang Province.
authors.forename: Wen
authors.initials: W
authors.lastname: Lv
authors.forename: Lihua
authors.initials: L
authors.lastname: Cheng
authors.forename: Baohua
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D017239:Paclitaxel