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Folate receptor alpha (FRalpha) is overexpressed on ovarian cancer cells and is a promising molecular target for ovarian cancer gene therapy, but there was still no related report. In this study, folate modified cationic liposomes (F-PEG-CLPs) for ovarian cancer gene delivery were developed for the first time. Folate-poly(ethylene glycol)-succinate-cholesterol (F-PEG-suc-Chol) was firstly synthesized and then used to prepare folate-targeted cationic liposomes/plasmid DNA complexes (F-targeted lipoplexes). F-targeted lipoplexes were prepared by post-insertion method, and displayed membrane structure by transmission electron microscopy observation with the diameter of 193 nm-200 nm and the zeta potential of 35 mV-38 mV. DNase degradation experiments showed that plasmid DNA could be effectively shielded by F-targeted lipoplexes in vitro. F-targeted lipoplexes could transfer gene into human ovarian carcinoma cell line SKOV-3, and 0.1% F-PEG-CLPs composed by DOTAP/Chol/mPEG-Chol/F-PEG-suc-Chol (50:45:5:0.1, molar ratio) had the highest transfection efficiency. The transfection activity of F-targeted lipoplexes could be competitively inhibited by free folic acid, demonstrating that folate-FRalpha interaction caused high transfection efficiency of F-targeted lipoplexes. The uptake mechanism of F-targeted lipoplexes was further validated on human oral carcinoma cell line KB and human liver carcinoma cell line HepG2. The concentration-dependent and time-dependent cytotoxicity of targeted material F-PEG-suc-Chol was observed by MTT assay on SKOV-3 cell and its application would not increase the cytotoxicity of F-targeted lipoplexes in SKOV-3 cells. All the data indicated that F-PEG-CLPs would be a promising gene vector targeting for ovarian cancer therapy.

To promote the application of methoxy poly(ethylene glycol)-cholesterol (mPEG-Chol), mPEG-Chol was used to prepare core-shell micelles encapsulating poorly water-soluble docetaxel (DTX-PM) by modified cosolvent evaporation method. Approaches to enhance DTX entrapment efficiency (EE) and minimize particle size were investigated in detail, including organic and aqueous phase composition, organic/aqueous phase ratio, and polymer concentration. In optimal formulation, micelles had higher EE (97.6%) and drug loading (4.76%) with the diameter of 13.76 ± 0.68 nm and polydispersity index of 0.213 ± 0.006. Transmission electron microscopy (TEM) showed that the micelles were spherical, and differential scanning calorimetry (DSC) analysis proved that DTX was successfully entrapped into mPEG-Chol micelles. The in vitro cytotoxicity experiments displayed that blank micelles had no effect on the growth of SKOV-3, BXPC-3, A549, and HepG-2 cells, demonstrating that mPEG-Chol was one of the biocompatible biomaterials. The half inhibition concentration of DTX-PM on SKOV-3, BXPC-3, A549, and HepG-2 cells were 10.08, 7.6, 28.37, and 125.75 ng/mL, respectively. DTX-PM had the similar antitumor activity to free DTX, indicating that mPEG-Chol was a promising micellar vector for hydrophobic drug delivery. In addition, this work provided a new and facile approach to prepare drug-loaded micelles with controllable performances., (Copyright © 2012 Wiley Periodicals, Inc.)

In this study, quercetin (QC) with cancer chemoprevention effect and anticancer potential was loaded into polymeric micelles of methoxy poly(ethylene glycol)-cholesterol conjugate (mPEG-Chol) in order to increase its water solubility. MPEG-Chol with lower critical micelle concentration (CMC) value (4.0 x 10(-7) M - 13 x 10(-7) M) was firstly synthesized involving two steps of chemical modification on cholesterol by esterification, and then QC was incorporated into mPEG-Chol micelles by self-assembly method. After the process parameters were optimized, QC-loaded micelles had higher drug loading (3.66%) and entrapment efficiency (93.51%) and nano-sized diameter (116 nm). DSC analysis demonstrated that QC had been incorporated non-covalently into the micelles and existed as an amorphous state or a solid solution in the polymeric matrix. The freeze-dried formulation with addition of 1% (w/v) mannitol as cryoprotectant was successfully developed for the long-term storage of QC-loaded micelles. Compared to free QC, QC-loaded micelles could release QC more slowly. Moreover, the release of QC from micelles was slightly faster in PBS at pH 5 than that in PBS at pH 7.4, which implied that QC-loaded micelles might be pH-sensitive and thereby selectively deliver QC to tumor tissue with unwanted side effects. Therefore, mPEG-Chol was a promising micellar vector for the controlled and targeted drug delivery of QC to tumor and QC-loaded micelles were also worth being further investigated as a potential formulation for cancer chemoprevention and treatment.

A sensitive method has been developed and validated for the determination of diverse groups of pharmaceuticals, steroid hormones, and hormone-like personal care products in sewage sludge. Samples were extracted by ultrasonic-assisted extraction followed by solid-phase extraction cleanup. For determination of estrogens and hormone-like phenolic compounds, sample extracts were further derivatized with dansyl chloride and purified with silica gel column chromatography to improve the analytical sensitivity. The chemicals were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in multiple-reaction monitoring mode. Recoveries ranged mostly from 63% to 119% with relative standard deviations within 15%. Method quantification limits were 0.1-3 ng g(-1) dry weight (dw) for sewage sludge. The method was applied to a preliminary investigation of pharmaceuticals and personal care products (PPCPs) in sewage sludge and sediment in the Pearl River Delta, South China. Triclosan, triclocarban, 2-phenylphenol, bisphenol A, and parabens were ubiquitously detected at 3.6-5088.2 ng g(-1) dw in sludge and 0.29-113.1 ng g(-1) dw in sediment samples, respectively. Estrone, carbamazepine, metoprolol, and propranolol were also frequently quantified in the sludge and sediment samples. The dewatering process caused no significant losses of these PPCPs in sewage sludge.

A simple and reliable method was developed for simultaneous determination of multi-class antibiotic residues in aquatic environment, including three fluoroquinolones (ofloxacin, norfloxacin, ciprofloxacin), three sulfonamides (sulfadiazine, sulfamethoxazole, sulfamethazine), chloramphenicol and trimethoprim. Samples were extracted and concentrated through hydrophilic-lipophilic balance (HLB) cartridges. Selected antibiotic compounds were determined by high performance liquid chromatography (HPLC) using internal standard quantification method. Antibiotics were separated on an Agilent XRD C18 column (150 mm x 3.0 mm, 3.5 microm) with a gradient elution using acetonitrile and 0.1% (v/v) formic acid in purified water at a flow rate of 0.25 mL/min and the column temperature of 25 degree C. Fluoroquinolones were quantified by fluorescence detection (FLD) and the others by ultraviolet detection at 280 nm. The recoveries for the antibiotics are ranging from 80% to 120% for spiked tap water, and 63% to 106% for urban river water samples, respectively, with relative standard deviation lower than 18%. The limits of quantification were 0.030-0.080 microg/L for surface waters. The method has been successfully applied to monitor the occurrence of antibiotic residues in the urban river waters from the Pearl River in Guangzhou. Sulfamethoxazole, ofloxacin, norfloxacin and ciprofloxacin were detected at mass concentrations ranging from 0.197 to 0.510 microg/L.