Interaction of the docetaxel with human serum albumin using optical spectroscopy methods

Docetaxel is a semi-synthetic product derived from the needles of the European yew. It is an antineoplastic agent belonging to the taxoid family. The interaction between docetaxel and human serum albumin (HSA) has been investigated systematically by the fluorescence quenching technique, synchronous fluorescence spectroscopy, ultraviolet (UV)-vis absorption spectroscopy, circular dichroism (CD) spectroscopy and Fourier transform infrared (FT-IR) under physiological conditions. Our fluorescence data showed that HSA had only one docetaxel binding site and the binding process was a static quenching procedure. According to the Van’t Hoff equation, the thermodynamic parameters standard enthalpy (ΔH⁰) and standard entropy (ΔS⁰) were calculated to be −41.07 KJ mol⁻¹ and −49.72 J mol⁻¹ K⁻¹. These results suggested that hydrogen bond was the predominant intermolecular force stabling the docetaxel-HSA complex. The data from the CD, FT-IR and UV-vis spectroscopy supported the change in the secondary structure of protein caused by the interaction of docetaxel with HSA.     

Co-delivery of docetaxel and doxorubicin using biodegradable PEG-PLA micelles for treatment of breast cancer with synergistic anti-tumour effects

Poly(ethylene glycol)-poly(lactic acid) copolymer, prepared by ring opening polymerization, was used as a single platform to co-deliver both hydrophilic doxorubicin and hydrophobic docetaxel (DTX) in a simulated physiological environment. The average size of the negatively charged drug loaded polymeric micelles were found to be 293 nm. The drug loading (%) and encapsulation efficiency (%) were calculated to be 1.21 and 59.0, respectively. The in vitro cytotoxicity test using MCF7 breast cancer cells was conducted using 1 × 10⁴ cells in 10% FBS and 1% antibiotic, and the absorbance of formazan was evaluated at 570 nm. Cell growth inhibition by MTT assay showed viability of 33% of the MCF7 cells after treatment with drug-loaded micelles for 48 h. Controlled release of drugs from the polymeric micelles indicated a burst release effect initially; whereas, 98% of drug could be released at pH 7.4 within a time period of 96 h. Time period for drug release shorten to 48 h only in simulated mild acidic pH (5.4) condition. The in vitro drug release study from micelles indicated synergistic cytotoxicity effect in human metastatic breast cancer MCF7 cell.     

Novel nanomicelles originating from hydroxyethyl starch-g-polylactide and their release behavior of docetaxel modulated by the PLA chain length

A novel drug carrier was synthesized through grafting polymerization of hydroxyethyl starch (HES) and d,l-lactide. By changing the molar ratio of HES and d,l-lactide, HES-g-PLA copolymers with different chain lengths of PLA can be obtained. Their chemical structures were characterized by FT-IR and ¹H NMR. Through self-emulsification combined with solvent evaporation, HES-g-PLAs self-assembled into micelles with uniform sizes ranging from 65 to 130 nm, depending upon the chain length of PLA. In vitro release profiles of docetaxel-loaded HES-g-PLAs meet first-order release kinetics via a mechanism of diffusion and polymer chain relaxation. The size of the micelles and the amount of drug loading can be controlled by varying the chain length of PLA. Another significant result is that release rates of docetaxel can be also modulated by changing the chain lengths of the PLA segments.     

Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel

The aim of this study was to design docetaxel-loaded nanostructured lipid carriers (DTX-NLC) to reduce toxicity and improve therapeutic efficacy. Docetaxel-loaded nanostructured lipid carriers (DTX-NLC) were prepared by the modified film ultrasonication–dispersion method. The DTX-NLC were characterized by particle size distribution, zeta potential and entrapment efficiency. In vitro cytotoxicity of DTX-NLC was evaluated by MTT assay against three human cancer cell lines and one murine malignant melanoma (B16). AnnexinV-FITC kit was used to measure the percentage of apoptosis induced by Duopafei^® or DTX-NLC. In vivo anti-tumor efficacy was evaluated in Kunming mice bearing murine malignant melanoma (B16). Compared with Duopafei^®, DTX-NLC revealed more cytotoxicity against A549 cells by inducing more apoptosis and more G2/M arrest. The inhibition rates of Duopafei^®, DTX-NLC (10 mg/kg) and DTX-NLC (20 mg/kg) were 42.74%, 62.69% and 90.36%, respectively, indicating that DTX-NLC could more effectively inhibit tumor growth. The results of the body weight variations of mice also showed that compared with Duopafei^®, DTX-NLC had lower toxicity during the therapeutic procedure. These results suggest that DTX-NLC may be a promising drug delivery system for cancer therapy. To our knowledge, this was the first report about DTX-NLC for murine malignant melanoma treatment.     

兔粪便中多烯紫杉醇的测定

建立了一种反相高效液相色谱法测定兔粪中多烯紫杉醇含量的方法。采用乙醚为萃取剂,液相色谱条件为:Phenomenex LUNA C18色谱柱(4.6mm×250mm,5μm);流动相为甲醇-乙腈-水(42:26:32,V/V/V);紫杉醇为内标;流速:1.0mL/min;检测波长:230nm;柱温:26℃。在浓度为1.38—55.0μg/g范围内,峰面积与浓度之间线性关系良好,相关系数为0.9993,平均回收率大于85.0%,相对标准偏差小于10.00%。结果表明,该方法具有操作简便、精密度和准确度较高的特点,可用于兔粪中多烯紫杉醇含量的测定。