聚乙二醇单甲醚-琥珀酰基半胱氨酸的合成

聚乙二醇单甲醚与琥珀酸酐开环酯化,N-羟基琥珀酰亚胺活化羧酸后与胱氨酸反应得二酰胺化合物,用二硫苏糖醇断二硫键后制得可用于制备长循环脂质体的聚乙二醇单甲醚-琥珀酰基半胱氨酸,并经基质辅助激光解吸电离飞行时间质谱确认其分子量,总收率23%.     

聚乙二醇单甲醚(2000)胆固醇琥珀酸酯包衣脂质体的研究

用聚乙二醇单甲醚 (2 0 0 0 )胆固醇琥珀酸酯 (PEGCHS)对脂质体进行包衣 ,以钙黄绿素(CF)为荧光探针 ,考察了不同PEGCHS加入量对脂质体包封率的影响 ,结果表明 ,随PEGCHS量的增加 ,包封率降低 .比较了包衣前后脂质体的体外、体内释放性 ,证明包衣后的脂质体 ,其体内半衰期大大延长 .     

壳聚糖/海藻酸钠自组装微球的制备及释药性能

目的利用壳聚糖(CS)聚阳离子及海藻酸钠(ALG)聚阴离子电解质的性质,在药物微球表面自组装形成多层包覆结构的壳聚糖载药微球,并研究组装层数、温度及盐离子浓度对自组装微球释药性能的影响。方法采用乳化交联法制备CS载四环素(TC)的药物微球,并在其表面交替自组装ALG及CS。利用IR测试技术及电极电位法进行表征。结果CS交联微球未破坏CS及TC的结构,CS与ALG以静电作用相结合。CS交联微球的载药量为40.2%,自组装六层的微球载药量为32%。组装后,药物释放时间延长,初期暴释现象得到极大改善,释药速率随组装层数的增加而下降,温度较高时组装完整,盐离子浓度存在较佳点。结论温度为60℃、盐离子浓度为0.5 mol.L-1、组装层数为四层的微球释药性能较佳。     

血卟啉单甲醚的制备

随着新药卟吩姆钠（ｐｒｏｆｉｍｅｒｓｏｄｉｕｍ）批准用于治疗复发性浅表乳头状膀胱癌、某些肺癌、食道癌［１］,光动力疗法治癌已引人瞩目。血卟啉单甲醚（１）是国内正在研究的光动力治癌剂［２,３］,与卟吩姆钠等不同的是,它不是组成不定的多种单体和聚合卟啉的...     

气相色谱法测定聚乙二醇单甲醚中2-甲氧基乙醇的残留量

目的:建立直接进样气相色谱法测定聚乙二醇单甲醚中2-甲氧基乙醇残留量的分析方法,为聚乙二醇单甲醚的质量控制提供参考依据。方法:采用Agilent DB-WAX(30 m×0.53 mm, 1.0μm)气相色谱柱,起始柱温40℃,保持5 min,以10℃·min^-1的速率升温至200℃,保持10 min。进样口温度200℃,氢火焰离子化检测器温度为250℃。样品以水溶解,液体进样。结果:2-甲氧基乙醇在0.5～2.0μg·mL^-1浓度范围内线性良好(r=0.995 7),平均回收率为(105.0±3.9)%(RSD=4%),检测限为0.3μg·mL^-1,定量限为0.5μg·mL^-1。2-甲氧基乙醇对照品水溶液在5 d内稳定。结论:本方法操作简便、环保,具有良好的系统适用性、线性、稳定性、精密度和准确度,可用于聚乙二醇单甲醚中2-甲氧基乙醇残留量的测定。     

纳米胶束载体聚乙二醇单甲醚聚乳酸嵌段共聚物中细菌内毒素动态显色定量方法的建立

目的: 建立纳米胶束载体聚乙二醇单甲醚聚乳酸嵌段共聚物细菌内毒素动态显色定量方法。 方法: 首先建立动态显色法测定细菌内毒素的标准曲线,并验证标准曲线的可靠性,考察样品对细菌内毒素检查的干扰情况,确定样品的最大无干扰浓度,随后验证方法的精密性和准确性,并进行初步应用。 结果: 标准曲线可靠性验证中,相关系数r＞0.99,标准曲线可靠。供试品用水稀释并添加内毒素标准品至供试品终浓度0.625mg.ml^-1(稀释40倍)及内毒素终浓度为0.25 Eu.ml^-1时,测定其回收率接近100%,供试品在该浓度对内毒素实验的干扰作用较小。方法的精密度和准确度验证中,标准曲线各浓度点测量结果的变异系数均＜7%,加入各浓度的内毒素标准品的测定结果的变异系数均＜5%,回收率在94%-112%之间。另外,日常检测3批供试品的内毒素含量均小于限值,回收率在97%-105%之间。结论: 动态显色法可用于定量检测纳米胶束载体聚乙二醇单甲醚聚乳酸嵌段共聚物的细菌内毒素。     

磷脂-壳聚糖自组装纳米粒的研究进展

目的:了解磷脂-壳聚糖自组装纳米粒的研究进展,为新型药物递送载体的研究和开发提供思路。方法:以"壳聚糖""磷脂""纳米粒""自组装""Chitosan""Lecithin""Phospholipid""Nanoparticles""Self-assembled"等为关键词,在中国知网、万方、维普、PubMed、Elsevier、SpringerLink等数据库中组合查询2002年-2018年11月发表的相关文献,对磷脂-壳聚糖自组装纳米粒的形成机制和微观结构、制备方法以及作为药物递送载体的应用等相关研究进行综述。结果与结论:共检索到相关文献499篇,其中有效文献34篇。带正电荷的壳聚糖与磷脂中负电荷基团通过静电相互作用自组装形成脂溶性致密内核、壳聚糖包裹带正电荷水化外壳的核壳结构纳米粒;采用常规的溶剂注入法制得的磷脂-壳聚糖自组装纳米粒,具有良好生物相容性,能促进药物渗透吸收和提高生物利用度等,在口服、经皮、眼部及鼻腔黏膜等给药系统具有广泛的应用前景。今后可考虑对壳聚糖或纳米粒表面进行结构修饰和功能性设计,并进一步探索和研究如何精准调控自组装纳米粒的微观结构、尺寸大小、药物分布以及功能等。     

小分子自组装纳米递药系统研究进展

生物纳米技术在药物递送领域的应用为高端创新制剂的研发注入了新动力,一系列新型纳米递药系统被相继开发乃至应用于临床。其中,由小分子药物或前药自组装形成的纳米递药系统因具有制备工艺简便、载药量超高和易于实现工业化生产等优势而备受关注,已成为纳米递药系统领域的一个重要分支。本文总结了小分子自组装纳米递药系统的最新研究进展。首先,对小分子前药自组装纳米递药系统进行介绍,包括两亲性、疏水性和二聚体小分子前药自组装纳米递药系统。其次,分别介绍小分子化学药物和小分子生物药物自组装纳米递药系统的最新进展。再者,对小分子杂化共组装纳米递药系统进行总结和分析,包括小分子纯药共组装纳米递药系统、小分子前药共组装纳米递药系统及小分子前药/小分子纯药共组装纳米递药系统。最后,讨论了小分子自组装纳米递药系统的合理设计、应用前景和临床挑战,以期为新一代纳米制剂的设计与构建提供参考。     

壳聚糖-磷脂自组装纳米粒载药系统的研究进展

本文综述了壳聚糖-磷脂自组装纳米粒作为新型药物递送系统的研究进展,阐述其自组装过程的关键机制,揭示了所得纳米粒独特的核-壳结构及该结构与包载药物之间的相互作用关系;总结了相关制备方法,并对经典的溶剂滴入法进行了详细说明.在此基础上,全面归纳了壳聚糖-磷脂自组装纳米粒在递送抗肿瘤药、抗炎药、多肽类药物、降脂药、抗菌药及基...     

基于中药活性成分自组装的无载体纳米制剂

传统中医药历史悠久,体系独特,技术完善.中药多以复方形式使用,可用于预防和治疗多种疾病.目前研究发现中药复方中的部分活性成分具有自组装特性,这些中药活性成分主要通过π-π堆积、静电作用、氢键和配位作用等非共价作用自组装形成纳米粒.基于中药活性分子自组装制备的复合纳米制剂可以提高难溶性中药活性分子的溶解度,改善它们在人体...     

Improvement of physicochemical and biopharmaceutical properties of theophylline by poly(ethylene glycol) conjugates

In the present paper two theophylline esters with poly (ethylene glycol) (PEG) and methoxy poly (ethylene glycol) (mPEG) were prepared. Quantitative yields of the pure products were obtained. Unlike the free drug, the drug-polymer conjugates are freely water-soluble at room temperature. In vitro release experiments in aqueous buffer demonstrate that both conjugates are stable in buffer of pH 7.4 and 1.2. In vivo release studies after oral administration of theophylline conjugates demonstrate a good release of parent drug.     

双氨基聚乙二醇的制备及分离纯化

聚乙二醇2000经氯代、叠氮化、氢化还原3步反应制得双氨基聚乙二醇（1）粗品,总收率57%.采用阳离子交换树脂,以不同浓度的乙酸盐缓冲液（pH 5.7）梯度洗脱,得到的1纯品采用IR、^1HNMR和HPLC等方法进行检测,并用高效分子排阻色谱法测定相对分子量.     

Preparation and characterization of novel poly(ethylene glycol) paclitaxel derivatives

Paclitaxel has been found to be very effective against several human cancers; one of the major problems with its use is its poor solubility, which makes necessary its solubilization with excipients that can determine allergic reactions often severe. The aim of this study is to develop highly water-soluble prodrugs of paclitaxel. For this purpose we prepared a series of new paclitaxel–poly(ethylene glycol) (PEG) conjugates that were characterized and evaluated for their in vitro stability and cytotoxicity. In particular, in order to modulate the release of paclitaxel from prodrugs, we prepared different compounds introducing PEG in the drug C2′ and/or C7 positions via ester or carbamate linkage. The conjugates were obtained in high purity and good yield. The carbamate prodrugs were highly stable in different media, while the compounds obtained linking PEG at C2′ position through an ester bond showed lower stability. Finally, the cytotoxic activity of the conjugates was evaluated on two cancer cell lines and the results showed that all the derivatives had a reduced cytotoxicity compared to that of paclitaxel.     

Clonazepam release from core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) triblock copolymers

The triblock copolymer based on poly(-caprolactone) (PCL) as hydrophobic part and poly(ethylene glycol) (PEG) as hydrophilic one was synthesized and characterized. Core-shell type nanoparticles of poly(-caprolactone)/poly(ethylene glycol)/poly(-caprolactone) (CEC) block copolymer were prepared by a dialysis technique. According to the amphiphilic characters, CEC block copolymer can self-associate at certain concentration and their critical association concentration (CAC) was determined by fluorescence probe technique. CAC value of the CEC-2 block copolymer was evaluated as 0.0030 g/l. CAC values of CEC block copolymer decreased with the increase of PCL chain length, i.e. the shorter the PCL chain length, the higher the CAC values. From the observation of transmission electron microscopy (TEM), the morphologies of CEC-2 core-shell type nanoparticles were spherical shapes. Particle size of CEC-2 nanoparticles was 32.3±17.3 nm as a monomodal and narrow distribution. Particle size, drug loading, and drug release rate of CEC-2 nanoparticles were changed by the initial solvents and the molecular weight of CEC. The degradation behavior of CEC-2 nanoparticles was observed by ¹H NMR spectroscopy. It was suggested that clonazepam (CNZ) release kinetics were dominantly governed by diffusion mechanism.     

Self-assembled polymeric nanoparticles of poly(ethylene glycol) grafted pullulan acetate as a novel drug carrier

Self-assembling nanospheres of hydrophobized pullulan have been developed. Pullulan acetate (PA), as hydrophobized pullulan, was synthesized by acetylation. Carboxymethylated poly(ethylene-glycol) (CMPEG) was introduced into pullulan acetate (PA) through a coupling reaction using N,N'-dicyclohexyl carbodiimide (DCC). A synthesized PA-PEG-PA (abbreviated as PEP) conjugate was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. Since PEP conjugates have amphiphilic characteristics in aqueous solution, polymeric nanoparticles of PEP conjugates were prepared using a simple dialysis method in water. From the analysis of fluorescence excitation spectra primarily, the critical association concentration (CAC) of this conjugate was found to be 0.0063 g/L. Observations by scanning electron microscopy (SEM) showed the spherical morphologies of the PEP nanoparticles. The particle size distribution of the PEP conjugates was determined using photon correlation spectroscopy (PCS) and the intensity-average particle size was 193.3 +/- 13.53 nm with a unimodal distribution. Clonazepam (CNZ), as a model drug, was easy to entrap into polymeric nanoparticles of the PEP conjugates. The drug release behavior was mainly diffusion controlled from the core portion.     

Improvement of warfarin biopharmaceutics by conjugation with poly(ethylene glycol)

One of the most used and useful polymers, poly(ethylene glycol) (PEG) was used as a carrier for warfarin. The drug–polymer conjugate was freely water soluble at room temperature. The hydrolytic stability of the PEG–warfarin was investigated at physiological pH and confirmed the stability of the conjugate. In vivo release studies demonstrated a good release of parent drug, without the initial high plasma level of warfarin.     

Stabilization and Controlled Release of Bovine Serum Albumin Encapsulated in Poly(D,L-lactide) and Poly(ethylene glycol) Microsphere Blends

Purpose. The acidic microclimate in poly(D, L-lactide-co-glycolide) 50/50 microspheres has been previously demonstrated by our group as the primary instability source of encapsulated bovine serum albumin (BSA). The objectives of this study were to stabilize the encapsulated model protein, BSA, and to achieve continuous protein release by using a blend of: slowly degrading poly(D, L-lactide) (PLA), to reduce the production of acidic species during BSA release; and pore-forming poly(ethylene glycol) (PEG), to increase diffusion of BSA and polymer degradation products out of the polymer. Methods. Microspheres were formulated from blends of PLA (Mw 145,000) and PEG (Mw 10,000 or 35,000) by using an anhydrous oil-in-oil emulsion and solvent extraction (O/O) method. The polymer blend composition and phase miscibility were examined by FT-IR and DSC, respectively. Microsphere surface morphology, water uptake, and BSA release kinetics were also investigated. The stability of BSA encapsulated in microspheres was examined by losses in protein solubility, SDS-PAGE, IEF, CD, and fluorescence spectroscopy. Results. PEG was successfully incorporated in PLA microspheres and shown to possess partial miscibility with PLA. A protein loading level of 5% (w/w) was attained in PLA/PEG microspheres with a mean diameter of approximately 100 m. When PEG content was less than 20% in the blend, incomplete release of BSA was observed with the formation of insoluble, and primarily non-covalent aggregates. When 20%-30% PEG was incorporated in the blend formulation, in vitro continuous protein release over 29 days was exhibited. Unreleased BSA in these formulations was water-soluble and structurally intact. Conclusions. Stabilization and controlled relaease of BSA from PLA/PEG microspheres was achieved due to low acid and high water content in the blend formulation.     

Investigation of solute permeation across hydrogels composed of poly(methyl vinyl ether‐co‐maleic acid) and poly(ethylene glycol)

Objectives Swelling kinetics and solute permeation (theophylline, vitamin B₁₂ and fluorescein sodium) of hydrogels composed of poly(methyl vinyl ether‐co‐maleic acid) (PMVE/MA) and poly(ethylene glycol) (PEG) are presented. Methods The effects of PMVE/MA and PEG 10 000 content on swelling behaviour (percentage swelling, the type of diffusion and swelling rate constant) were investigated in 0.1 m phosphate buffer. Network parameters, such as average molecular weight between crosslinks (M_c) and crosslink density, were evaluated. Key findings The percentage swelling and M_c of hydrogels increased with decrease in PMVE/MA content, where the water diffusion mechanism into the hydrogels was Class‐II type. In contrast, increase in PMVE/MA content caused an increase in the crosslink density. Permeation of theophylline, vitamin B₁₂ and fluorescein sodium, with increasing hydrodynamic radii, was studied through the equilibrium swollen hydrogels composed of PMVE/MA and PEG. In general, the permeability and diffusion coefficients of all three solutes decreased with increase in the PMVE/MA content. In addition, permeability and diffusion coefficient values increased with decreases in the hydrodynamic radii of the solute molecules. Conclusions The hydrogels have shown a change in swelling behaviour, crosslink density, M_c and solute permeation with change in PMVE/MA content, thus suggesting a potential application in controlled drug‐delivery systems.     

Poly(ethylene glycol)-modified Nanocarriers for Tumor-targeted and Intracellular Delivery

The success of anti-cancer therapies largely depends on the ability of the therapeutics to reach their designated cellular and intracellular target sites, while minimizing accumulation and action at non-specific sites. Surface modification of nanoparticulate carriers with poly(ethylene glycol) (PEG)/poly(ethylene oxide) (PEO) has emerged as a strategy to enhance solubility of hydrophobic drugs, prolong circulation time, minimize non-specific uptake, and allow for specific tumor-targeting through the enhanced permeability and retention effect. Furthermore, PEG/PEO modification has emerged as a platform for incorporation of active targeting ligands, thereby providing the drug and gene carriers with specific tumor-targeting properties through a flexible tether. This review focuses on the recent developments surrounding such PEG/PEO-surface modification of polymeric nanocarriers to promote tumor-targeting capabilities, thereby enhancing efficacy of anti-cancer therapeutic strategies.