Thermoresponsive Reversible Unimer Micelles of Amphiphilic Fluorinated Copolymers

Amphiphilic fluorinated copolymers PEGMAx-co-FAy and TEGMAx-co-FAy are prepared by activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). All polymers present a reversible thermoresponsive lower critical solution temperature-type behavior, and a cloud point temperature (T_c) in the range of 30–60 °C strictly dependent on the length of the oxyethylene side chain, the content of the hydrophobic counits, and the concentration of the solution. Combined small angle X-ray scattering (SAXS) and dynamic light scattering measurements are used to study the self-assembly behavior in water, organic solvents (tetrahydrofuran [THF] and dimethylformamide [DMF]), and a fluorinated solvent (hexafluorobenzene [HFB]). SAXS confirms the formation of compact-globular single-chain self-folded unimer micelles in water below T_c, which generally presents small hydrodynamic diameters (D_h ≤ 8 nm) as a result of the folding of the hydrophobic perfluorohexylethyl acrylate counits. The copolymers are also able to form reverse unimer micelle in HFB. The copolymers are not able to self-assemble in unimer micelles in THF or DMF solutions, in which they adopt conventional random coil conformations.     

Measurement of Glass Transition Temperatures of Freeze-Concentrated Solutes by Differential Scanning Calorimetry

Thermal analysis of aqueous solutions in which the solute does not crystallize immediately upon freezing was carried out to define the effects of experimental parameters on thermograms in the glass transition region. The intensity of enthalpy relaxations in the glass transition region is related to both the rate of cooling and the rate of heating through the glass transition region—slow cooling or slow heating increases the extent of structural relaxation in the glassy state and increases the intensity of the endotherm. Plots of the logarithm of heating rate versus l /Tg are linear, and activation enthalpies for structural relaxation are in the range of 210–350 kJ/mol. For polymeric solutes, both the activation enthalpies for structural relaxation and the heat capacity change accompanying the glass transition increase with increasing molecular weight of the solute. Molecular weight dependence of the observed midpoint of the glass transition agrees with the Fox–Flory relationship. Results are compared and contrasted with glass transitions in solid polymers and with the glass transition of hyperquenched water. Practical implications for characterization of formulations intended for freeze-drying are discussed.     

Use of Stable Isotopes for Evaluation of Drug Delivery Systems: Comparison of Ibuprofen Release in Vivo and in Vitro from Two Biphasic Release Formulations Utilizing Different Rate-Controlling Polymers

Certain delivery systems are intended to release the active ingredient in different phases to obtain the desired therapeutic effect. For these formulations, such as a bilayer tablet, it is desirable to distinguish and measure the release of drug from the different phases simultaneously. Mass spectrometric methods were developed to measure three ibuprofen isotopomers in serum and two in dissolution fluid. The analytical methods were linear (r 0.992) over the concentration range of interest and recovery was greater than 99.2% for all isotopomers. Coadministration of [²H₀]ibuprofen, [²H₄]ibuprofen, and [²H₇]ibuprofen to male beagles demonstrated that the isotopomers were bioequivalent and verified the absence of any kinetic isotope effect due to deuterium incorporation (p = 0.286). These methods were then used to evaluate a bilayer tablet formulation composed of an immediate release layer of 100 mg [²H₄]ibuprofen and a sustained release layer with a drug load of 300 mg [²H₀]ibuprofen. Two different rate-controlling polymer matrices that provided similar in vitro dissolution profiles were compared in the sustained release phase, while the immediate release formulation remained the same. In male beagles, the HPMC matrix delivered a significantly greater amount of ibuprofen (p < 0.05). The AUC was threefold greater for HPMC (1067 ± 437 nmole * h/ml) versus EUDRAGIT^® (320 ± 51), and C_max was nearly four times greater (145 ± 62.1 nmole/ml for HPMC versus 37.9 ± 14.4 for EUDRAGIT^®). Although T_max for HPMC (3.4 ± 1.9 h) lagged behind EUDRAGIT^® (2.0 ± 0.82 h), the difference was not significant (p > 0.05). The immediate release layer was absorbed to the same extent as an oral solution (containing [²H₇]ibuprofen) that was administered concomitantly with the bilayer tablet. Using the stable isotope markers also demonstrated that the release rates of the two layers were independent of each other, both in vivo and in vitro. Stable isotope techniques are a useful tool in the development of biphasic release formulations since they can be used to determine proper drug load of each phase as well as the appropriate rate of release.     

In Vivo Evaluation of a Colon-Specific Drug Delivery System: An Absorption Study of Theophylline from Capsules Coated with Azo Polymers in Rats

Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coatings for colon-specific drug delivery. The gastrointestinal absorption of theophylline from capsules coated with the azo polymers was examined in the proximal part of the small intestine and the cecum of male Wistar rats. The capsules were surgically inserted in the region of interest. The plasma concentration of the drug was higher when the capsules were inserted in the cecum as compared to the small intestine. The appearance of theophylline in the plasma when capsules were administered in the small intestine can be attributed to simple diffusion of the drug through the swollen polymer coating. Release and absorption from the cecum is the combined result of diffusion and degradation of the azo polymer coatings by bacterial azo reductase.     

磷脂聚合物在医药学中的应用

目的在简介磷脂的基础上 ,概括了磷脂类似物和磷脂聚合物的合成方法及其在医药领域中的应用。方法在参阅国内外相关文献的基础上 ,进行分析、整理和归纳。结果磷脂聚合物的合成方法已经发展的比较成熟 ,但是在医药方面的应用主要限于磷脂聚合物型脂质体、聚乙二醇(PEG)修饰型脂质体和磷脂修饰型聚合物。结论具有两亲性和生物相容性的磷脂及其聚合物在医药领域具有广泛的发展前景     

医用高分子材料的Ames试验研究

男性绝育药输精管粘堵剂、男性避孕材料水凝胶、医用组织复合膜、胶原膜、复合缝线、铬制复合型可吸收缝线、药物载体聚乳酸、固定材料聚酯醚等８种医用高分子材料，经Ａｍｅｓ试验的标准菌株ＴＡ９７、ＴＡ９８、ＴＡ１００、ＴＡ１０２测试，均未诱发回复突变菌落数增加，对Ａｍｅｓ试验菌株无诱发突变作用。用这种方法测试不同类型的医用高分子材料是可行的。     

天然高分子磁微球作为靶向制剂的研究进展

磁性微球作为靶向药物载体有利于提高药物疗效，降低药物的毒副作用，为化疗药物的临床应用开辟了新途径。文章着重综述和评价了以天然高分子材料为载体的磁性微球的制备和应用，并对相关研究工作中存在的问题提出了看法。     

配合物分子印迹聚合物的识别性能

以乙酸镍和2,2′-联吡啶配合物为模板、4-乙烯吡啶为功能单体、乙二醇二甲基丙烯酸酯为交联剂,合成了具有类似金属螯合抗体结合位点的金属配合物印迹聚合物,系统研究了金属离子对模板聚合物选择性结合2,2′-联吡啶的调节作用。结果表明:印迹聚合物对N i(Ⅱ)-2,2′-联吡啶配合物有选择性识别能力。采用Scatchard模型评价分子印迹聚合物的结合特性,得到高亲和力结合位点的平衡离解常数Kd1=0.082 mm o l/L,表观最大结合量Qm ax1=82.2μm o l/g,低亲和力结合位点的Kd2=0.400 mm o l/L,Qm ax2=91.3μm o l/g。     

荧光定量聚合酶链反应诊断结核病临床应用研究

目的探讨荧光定量聚合酶链反应（FQ-PCR）技术诊断结核病临床应用价值。方法应用FQ-PCR技术检测患者痰、外周血、体液（包括各种渗出液及脑脊液）中结核分枝杆菌DNA（TB-DNA），并与定性PCR、常规细菌学涂片法和培养法比较。结果112例结核病患者FQ-PCR、定性PCR、涂片法和培养法检测各类标本阳性率为59．82％，88．82％，25．89％，29．46％，非结核组43例FQ-PCR法阳性率是2．32％，PCR法是18．60％，FQ-PCR检测其标本TB-DNA的特异性为97．67％，敏感度为59．82％，阳性预测值为98．53％。结论FQ-PCR检测TB-DNA是一种快速简便、敏感性、特异性、可信性较高的方法，对诊断结核病具有临床意义，且适用于临床检验实验室，其含量变化对判断疗效有一定的提示作用。     

Biocompatibility of implant materials: A review and scanning electron microscopic study

The evolution of various plastic materials used in the manufacture of intraocular lenses is reviewed, with special reference to the problem of biocompatibility of lens haptic materials. To date, polypropylene has been found and continues to be a highly effective, relatively inert material, providing good surgical results. However, the present study and other morphologic and chemical studies have provided evidence that indicates long-term alteration of polypropylene may occur. For this reason we believe that further studies of this particular polymer are warranted. Also, a continuing search and trial of other plastics to discover an equivalent or even more efficacious haptic material seems desirable. There is a need for careful long-term follow-up of patients after intraocular lens implantation, particularly of young patients.