title: A novel monomethoxy polyethylene glycol-polylactic acid polymeric micelles with higher loading capacity for docetaxel and well-reconstitution characteristics and its anti-metastasis study.
abstract: Docetaxel (DTX) is hydrophobic, and its available formulations (Taxotere(®) & Duopafei(®)) require Tween80 and ethanol vehicle to allow parental administration. DTX-loaded poly(D,L-lactide)-b-polyethylene glycol-methoxy (mPEG-b-PDLLA) polymeric micelle (PM) is a Tween80-free formulation of DTX, which has been extensively studied but rarely involved with industrialization issues. In this work, novel DTX-PM with improved loading capacity and well-reconsitution ability was developed. The freeze-dried DTX-PM was analyzed by HPLC, transmission electron microscopy (TEM) and dynamic light scattering (DLS) to determine the DTX loading, micelle morphology and size respectively. The in vitro cytotoxic activity of DTX-PM in 4T1 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the corresponding in vivo study was assessed in BALB/c mice bearing 4T1 tumor through intravenous administration. The DTX-loading and efficiency into the micelles were 20.74±1.23% and 93.7±1.03% respectively, which was much higher than ever reported PM. The DTX-PM was spherical with a mean particle size of 16.62±0.31 nm, which suggested that they were able to selectively accumulate in solid tumors by enhanced permeability and retention (EPR) effect. Another important characteristic of DTX-PM is the long term storage and reuses as aqueous injection solution. Many kinds of lyoprotectants were also investigated and dextrose was found to an excellent one. Compared with Duopafei(®), DTX-PM showed better cytotoxicity and anti-metastasis ability against 4T1 cells in vitro and in vivo. In conclusion, DTX-PM significantly enhanced drug-loading capacity of DTX and had well-reconsitution ability, which could be a promising drug delivery system for clinic.
authors.affiliation: State Key Laboratory of Bioactive Substance and Functions of Natural Medicines, Chinese Academy of Medical Sciences, Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Li
authors.forename: Feifei
authors.initials: F
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Mingji
authors.initials: M
authors.lastname: Jin
authors.forename: Zhonggao
authors.initials: Z
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide)