Synthesis and Evaluation of Novel Polyester-Ibuprofen Conjugates for Modified Drug Release

Ibuprofen was conjugated at different levels to a novel polyester, poly(glycerol-adipate-co-ω-pentadecalactone) (PGA-co-PL), via an ester linkage to form a prodrug. The conjugates were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), infrared (IR), gel permeation chromatography (GPC), ultraviolet (UV), and high-performance liquid chromatography (HPLC). The conjugates had a molecular weight between 18 and 24 kDa, and there was a suppression of the free hydroxyl groups within the conjugated polymer. DSC scans showed a lowering of the melting point (T_m) when compared with the polyester alone and a difference in the number and area of T_m peaks. Drug release studies showed an initial burst release (13–18%) followed thereafter by very slow release (maximum 35% after 18 days). Continuous work may produce ester-linked conjugates that are sufficiently labile to allow for complete release of ibuprofen over the time period studied.     

Fabrication of thermoplastic polyester elastomer/layered zinc hydroxide nitrate nanocomposites with enhanced thermal,mechanical and combustion properties

The objective of this study is to explore the potential of layered zinc hydroxide nitrate modified with sodium benzoate as nanoparticle in thermoplastic polyester elastomer (TPEE). The organically modified zinc hydroxide nitrate was compounded with TPEE using solution blending method. The nanocomposite structure was characterized by means of X-ray diffraction and transmission electron microscopy. The results showed that the nanoparticle was homogenously dispersed in TPEE matrix, and partially exfoliated structure was formed. The thermal behavior, mechanical and thermal combustion properties of the novel nanocomposite were studied respectively through differential scanning calorimeter (DSC), dynamic mechanical analysis (DMA) and microscale combustion calorimeter (MCC). For the nanocomposite containing 7 wt% nanoparticle, the crystallization temperature evaluated by DSC was increased by 10 °C. The storage modulus at −95 °C measured by DMA was improved by around 26%. The heat release capacity (an indicator of a material fire hazard) from MCC testing was reduced by about 56% (compared to the results of neat TPEE).     

Amphiphilic polymer–drug conjugates based on acid-sensitive 100% hyperbranched polyacetals for cancer therapy

A new type of acid-sensitive 100% hyperbranched polyacetals (HBPA) was synthesized, which could be completely degraded into small molecules under acidic environment and avoid the accumulative toxicity in vivo. The AB₂ monomer was synthesized by 4-carboxybenzaldehyde and 2-bromoethanol. The bulk polycondensation was carried out in vacuum environment to remove water byproduct. The massive terminal aldehyde groups of HBPA were conjugated with mPEG-NH₂ and doxorubicins to form amphiphilic acid-sensitive polymer–drug conjugates (DOX-HBPA-PEG). The stability of the micelles of DOX-HBPA-PEG was evaluated by DLS at different pH value in phosphate buffer saline (PBS). The DOX release in vitro showed that the cumulative release rate was 14.51% in pH 7.4 PBS after 24 h and the cumulative release rate was 48.56% in pH 6.0 PBS after 24 h. The results of cell viability of DOX-HBPA-PEG and HBPA-PEG showed that the polymer–DOX conjugates were effective drug delivery systems. The uptake process of DOX-HBPA-PEG by A549 cells showed that the micelle was totally swallowed in 1 h later. The controllable drug release nature, stability, biocompatibility and completely degradable structures (acid-sensitive) make them to be promising drug delivery systems.     

Synthesis and characterization of saturated polyester and nanocomposites derived from glycolyzed PET waste with varied compositions

Saturated polyester resin, derived from the glycolysis of polyethyleneterephthalate (PET) was examined as an effective way for PET recycling. The glycolyzed PET (GPET) was reacted with the mixture of phthalic anhydride and ethylene glycol (EG) with varied compositions and their reaction kinetic were studied. During polyesterification of GPET, acid and EG, the parameters like degree of polymerization (DP _n ), extent of reaction (p) acid value and hydroxyl values were measured. The thermomechanical properties and the morphologies of the saturated polyester nanocomposites were examined by using a differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), wide angle X-ray diffraction (WAXRD) and transmission electron spectroscopy (TEM). There were significant differences observed in ${T}_{\textrm{g}}$ , ${T}_{\textrm{m}}$ and ${T}_{\textrm{c}}$ before and after addition of GPET and clay content. Nanocomposites with lower content of organoclay showed intercalated morphology while by increasing the amount of organoclay, the exfoliated morphology was more prevalent. Water vapour transmission (WVT) was determined for saturated polyester nanocomposite sheets according to ASTM E96-80.     

PVK/MWNT electrodeposited conjugated polymer network nanocomposite films

The facile preparation of poly (N-vinyl carbazole) (PVK) and multiwalled carbon nanotubes (MWNTs) solution and conjugated polymer network (CPN) nanocomposite film is described. The stable solutions of PVK/MWNT were prepared in mixed solvents by simple sonication method, which enabled successful deaggregation of the MWNTs with the polymer matrix. MWNT was most effectively dissolved in N-cyclohexyl-2-pyrrolidone (CHP) compared to other solvents like N-methyl pyrrolidone (NMP), dimethyl formamide, and dimethyl sulfoxide (DMSO). The composite solution was relatively stable for months with no observable precipitation of the MWNTs. Thermogravimmetric analysis (TGA) revealed the thermal stability of the nanocomposite while the differential scanning calorimetry (DSC) showed an increasing melting (T(m)) and glass transition (T(g)) temperatures as the fraction of the MWNTs in the nanocomposite was increased. Cyclic voltammetry (CV) allowed the electrodeposition of the nanocomposite film on indium tin oxide (ITO) substrates and subsequent cross-linking of the carbazole pendant group of the PVK to form CPN films. Ultraviolet-visible (UV-vis), fluorescence, and Fourier transform infrared (FTIR) confirmed film composition while atomic force microscopy (AFM) revealed its surface morphology. Four-point probe measurements revealed an increase in the electrical conductivity of the CPN nanocomposite film as the composition of the MWNTs was increased: 5.53 × 10(-4) (3% MWNTs), 0.53 (5%), and 1.79 S cm(-1) (7%). Finally, the interfacial charge transfer resistance and ion transport on the CPN nanocomposite film was analyzed by electrochemical impedance spectroscopy (EIS) with a measured real impedance value of ～48.10 Ω for the 97% PVK and 3% MWNT ratio of the CPN nanocomposite film.     

Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir

Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug–polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00?s^?1 at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at T_g depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.     

Development of biodegradable microcapsules as carrier for oral controlled delivery of amifostine

The primary objective of this project was to develop a biodegradable, orally active controlled-release formulation of amifostine. Development of such a formulation will mark an important advancement in the areas of chemoprotection and radioprotection. Biodegradable microcapsules of amifostine were prepared using poly(lactide/glycolide) (PLGA 50:50). The microcapsules were prepared by solvent evaporation technique. Amifostine-loaded microcapsules were evaluated for particle size, surface morphology, thermal characteristics, and drug release. Particle size and surface morphology were determined using scanning electron microscopy (SEM). Thermal characterization was conducted using differential scanning calorimetry (DSC). In vitro release study was performed at 37°C using phosphate buffer (pH 7.4). Amifostine release was calculated by measuring the amount of drug remaining within the microcapsules at a specific sampling time. The amount of amifostine in the samples was determined by high-performance liquid chromatography (HPLC) using an electrochemical detector. The yield of microcapsules was 75%. Scanning electron microscopy pictures revealed that the particles were nearly spherical and smooth with an average size of 54 µm. Differential scanning calorimetry thermograms showed that microcapsules loaded with amifostine have a glass transition at 39.4°C, and the melting endotherm of amifostine was absent. The absence of a melting endotherm for amifostine was an indication that amifostine was not in the crystalline state in the microcapsules, but rather in the form of a solid solution in PLGA. Approximately 50% amifostine was released during the first 6 hr of the in vitro release study. The drug, however, continued to release over the observed period of 12 hr during which 92% amifostine was released.     

Synthesis and photovoltaic properties of new conjugated polymers based on benzo[1,2-b:4,5-b']dithiophene

New conjugated polymers based on benzo[1,2-b:4,5-b']dithiophene, poly(benzo[1,2-b:4,5-b'] dithiophene-alt-bithiophene) (PBT-2T) and poly(benzo[1,2-b:4,5-b']dithiophene-alt-terthiophene) (PBT-3T), have been synthesized via the Stille coupling reaction and their optical and electrochemical properties were characterized by UV-vis, photoluminescence (PL) and cyclic voltammetry (CV) measurements. Compared to PBT-2T, PBT-3T film showed clearly red-shifted UV-visible absorption and PL spectra with maxima at 511 and 653 nm, respectively. Especially, PBT-3T containing terthiophene showed very small optical band gap of 1.65 eV. The PBT-2T and PBT-3T showed the power conversion efficiencies of 0.25% and 0.34%, respectively, under AM 1.5 (100 m/cm2).     

超支化糖苷聚合物的合成及生物基质共混膜性能

单糖分子为原料,Koenigs-Knorr法合成一种带羧基和多羟基的糖苷衍生物,以此糖苷衍生物为单体制备超支化聚酯。用傅里叶变换红外光谱、核磁共振波谱、凝胶渗透色谱、差示扫描量热分析和热重分析表征中间产物和超支化聚酯结构。超支化聚酯与聚乳酸共混制备复合膜,扫描电镜观测复合膜的相容性,拉力试验测试复合膜的力学性能,差示扫描量热分析复合膜的热性能,接触角测量仪测试复合膜的润湿性。结果表明,成功合成了超支化聚酯目标产物,超支化聚酯的相对分子质量随代数的增加而上升,支化度较高,热稳定性较好。超支化聚酯与聚乳酸相容性良好,共混之后聚乳酸的力学性能、热性能及润湿性均有提高。     

Conjugation of luminescent quantum dots with antibodies using an engineered adaptor protein to provide new reagents for fluoroimmunoassays

We describe the preparation and characterization of bioinorganic conjugates made with highly luminescent semiconductor CdSe-ZnS core-shell quantum dots (QDs) and antibodies for use in fluoroimmunoassays. The conjugation strategy employs an engineered molecular adaptor protein, attached to the QDs via electrostatic/hydrophobic self-assembly, to link the inorganic fluorophore with antibodies. In this method, the number of antibodies conjugated to a single QD can be varied. In addition, we have developed a simple purification strategy based on mixed-composition conjugates of the molecular adaptor and a second two-domain protein that allows the use of affinity chromatography. QD-antibody conjugates were successfully used in fluoroimmunoassays for detection of both a protein toxin (staphylococcal enterotoxin B) and a small molecule (2,4,6-trinitrotoluene).     

Preparation,characterization, and in vivo evaluation of injectable long-acting curcumin microcrystal

In this research, curcumin microcrystal was produced using the wet milling method, and its pharmacokinetic behavior was compared after intramuscular (i.m.) and oral administration. The effects of milling time on the prepared curcumin microcrystal were investigated. Curcumin microcrystal was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), FTIR, and in vitro dissolution. The results showed that there were no obvious changes in the crystal structure between bulk curcumin and curcumin microcrystal. Significantly higher dissolution rate from curcumin microcrystal (83.5%) at 90?min was observed, compared with that of bulk curcumin (74.1%). Furthermore, the in vivo pharmacokinetic behavior and muscular irritation after i.m. administration were also evaluated. The results showed that the release of curcumin lasted for 1 week by processing into microcrystal. The histological examination implied that curcumin microcrystal was safe for i.m. injection and was appropriate for the i.m. delivery of curcumin.     

低温固化粉末涂料用不饱和超支化聚氨酯低聚物的合成

以三羟甲基丙烷、超支化聚酯、季戊四醇和甘露醇为多羟基核,以甲苯-2,4-二异氰酸酯和甲基丙烯酸羟乙酯封端,采用溶液聚合的方法合成了4种不饱和的超支化聚氨酯低聚物。讨论了不同因素对以季戊四醇为核的产物反应的影响,发现反应温度可以调节产物的热稳定性。用红外光谱仪、差示扫描量热仪和凝胶渗透色谱仪对产物进行了表征,结果表明这4种不饱和的超支化聚氨酯的玻璃化转变温度Tg在13.5～57.4℃之间,尤其是以季戊四醇为核的产物的Tg为57.4℃,数均分子量Mn为1674,可用于低温固化粉末涂料。     

聚酯含量对PBT/PET/PA-6三元共混物性能影响

采用ＤＳＣ、ＳＥＭ等方法对ＰＢＴ／ＰＥＴ／ＰＡ６三元共混物中聚酯含量的变化与共混物性能之间的关系进行了研究。实验结果表明,共混物中ＰＥＴ含量的增加有利于提高该三元共混物的热性能和结晶性能;另外,ＰＢＴ含量的增加则大大提高了共混物的抗冲击能力。     

Purity Determination and Uncertainty Evaluation of Acrylonitrile by Gas Chromatography and Differential Scanning Calorimetry

Methods of gas chromatography and differential scanning calorimetry (DSC) were used to determine the purity of acrylonitrile. In the method of gas chromatography, the organic impurities were determined using benzene as external standard, the contents of moisture were determined using the Karl Fisher method, and the inorganic elements were determined using ICP-MS method. The purity determined using gas chromatography was 99.32% (g/g) with an extended uncertainty of 0.42% (k?=?2), and that determined using DSC method was 98.88% (g/g) with an extended uncertainty of 1.07% (k?=?2). The uncertainty evaluation of purity demonstrated that the accuracy of the gas chromatography method is better than that of DSC method.     

Synergistic effects of SPR and FRET on the photoluminescence of ZnO nanorod heterostructures

Solution-grown ZnO nanorods (NRs) were successfully conjugated with CdSe/ZnS quantum dots (QDs) and Ag nanoparticles (NPs) to suppress intrinsic defect emission and to enhance band-edge emission at the same time. First, high-density and high-crystallinity ZnO NRs of diameter 80–90 nm and length 1.2–1.5 μm were grown on glass substrates using a low-temperature seed-assisted solution method. The as-synthesized ZnO NRs showed sharp photoluminescence (PL) band-edge emission centered at ～377 nm together with broad defect emission in the range of ～450–800 nm. The ZnO NRs were decorated with CdSe/ZnS QDs and Ag NPs, respectively, by sequential drop-coating. The PL of CdSe/ZnS QD||ZnO NR conjugates showed that ZnO band-edge emission decreased by 73.8% due to fluorescence resonance energy transfer (FRET) and charge separation between ZnO and CdSe/ZnS by type II energy band structure formation. On the other hand, Ag NP||CdSe/ZnS QD||ZnO NR conjugates showed increased band-edge emission (by 25.8%) and suppressed defect emission compared to bare ZnO NRs. A possible energy transfer mechanism to explain the improved PL properties of ZnO NRs was proposed based upon the combined effects of FRET and surface plasmon resonance (SPR).     

pH-independent dissolution enhancement for multiple poorly water-soluble drugs by nano-sized solid dispersions based on hydrophobic–hydrophilic conjugates

The objective of this study was to achieve an optimal formulation of hydrophilic–hydrophobic conjugates for nano-sized solid dispersions (SDs) with enhanced dissolution of multiple drugs in different gastrointestinal (GI) tract environments. A new conjugate powder with an optimized process was used to fabricate SDs that contained three poorly water-soluble drugs that were also poorly soluble in different dissolution media. The self-assembled nanoparticle formation, drug crystallinity and SD molecular interactions were investigated by measuring the particle size during dissolution testing and physicochemical property analysis (powder X-ray diffraction and Fourier transform infrared spectroscopy). Drug release studies indicated that SD containing conjugated powder significantly improved the dissolution rates of these poorly water-soluble drugs in the GI tract. In addition, particle size analysis showed nano-sized particles in the dissolution media in the early stage with a tendency to reduce smaller particles over time. Physicochemical characterizations demonstrated almost amorphous drug states and hydrogen bonding interactions between the drugs and conjugates in the SD. This study optimized a promising material for SD, and the material was shown to have a promising performance under various pH medium conditions with poorly water-soluble drugs.     

Preparation and characterization of camptothecin solid lipid nanoparticles

Camptothecin (CA), an antitumor drug, was incorporated into solid lipid nanoparticles (SLNs) prepared by high-pressure homogenization. A Taguchi orthogonal experimental design was used to study the influence of four different variables, with each variable having three value levels on nanoparticle size. Analysis of variance (ANOVA) has been used to evaluate the preparation of CA-SLNs and perform product optimization. The optimized CA-SLNs suspension was lyophilized using mannitol and glucose as cryoprotectants. The physicochemical characteristics of CA-SLNs were evaluated using transmission electron microscopy (TEM), electrophoresis, and differential scanning calorimetry (DSC). The release of camptothecin from CA-SLNs in various media was evaluated using a high-performance liquid chromatography (HPLC) method. The results showed that the concentration of emulsifier and the homogenization pressure had a significant influence on the particle size. The optimized CA-SLNs had an average diameter of about 200 nm, exhibited monodispersity with Dw/Dn of 1.06, and carried a negative charge. The optimal cryoprotectants consisted of 10% mannitol and 5% glucose in nanoparticle suspension. Lyophilized product was reconstituted in distilled water within 0.5 min without change of nanoparticle size. Camptothecin might exist in an amorphous state in SLNs. In vitro results showed that drug release was achieved for up to one week, and the released camptothecin quickly changed to open carboxylate form in the biological pH phosphate buffer. The results indicate that SLNs might be good potential sustained-release delivery vehicles for camptothecin or other lipophilic drugs.     

Determination of benzo[a]pyrene sulfate conjugates from benzo[a]pyrene-treated cells by continuous-flow fast atom bombardment mass spectrometry

The level of certain water-soluble hydrocarbon conjugates, such as benzo[a]pyrene sulfates (BP-SO4), is a direct measure of carcinogenic polycyclic aromatic hydrocarbon metabolism and an indication of exposure. A new method, based on continuous-flow high-resolution fast atom bombardment mass spectrometry, has been developed for the analysis of BP-SO4 in the medium of cell cultures treated with benzo[a]pyrene. An organic solvent extract of medium from cultures of the human hepatoma cell line (HepG2) was fractionated by reversed-phase SEP-PAK chromatography and microbore high-performance liquid chromatography (HPLC). The HPLC fraction containing BP-SO4 was collected, dried, and injected into a stream of acetonitrile/water/glycerol that was continuously flowing to the tip of the sample probe which was being bombarded continuously by a beam of high-energy xenon atoms. Molecular anions of BP-SO4 (m/z 347) desorbed from the liquid were analyzed by a high-resolution (m/delta m 5000) mass spectrometer and recorded as a function of time. As little as 1.5 pg of BP-SO4 could be detected with a S/N ratio of 8. The mass spectrometer response was linear with respect to the quantity of BP-SO4 injected over the range from 15 to 625 pg. The results obtained with this method show that the HepG2 cultures metabolized 3% of the benzo[a]pyrene into the BP-SO4 conjugate in 24 h. This procedure, which was used to detect and quantify directly BP-SO4 in culture medium without the use of a radiolabeled precursor, should be generally applicable for analyses of sulfated conjugates resulting from the metabolism of different hydrocarbons.     

端叠氮基超支化聚酯的合成与表征

以三羟甲基丙烷为核、对甲苯磺酸为催化剂,2,2-二羟甲基丙酸缩聚为端羟基超支化聚酯,端羟基先后经磺酰化改性和叠氮基取代后得到端叠氮基超支化聚酯。利用红外光谱、核磁共振、元素分析、凝胶色谱等方法对目标产物进行了结构表征和确认;在此基础上,对目标产品进行了热重(TG)和差示扫描量热(DSC)表征。结果表明:端叠氮基超支化聚酯的支化度为0.45;热分解分为两个阶段,分别是端叠氮基热分解(249.4℃)和主链热分解(350℃);玻璃化转变温度为-55.2℃。     

Mechanical properties of chemically-treated hemp fibre reinforced sandwich composites

In this study, hemp fabrics were used as reinforcements with polyester resin to form composite skins while short hemp fibres with polyester as a core for making composite sandwich structures. To improve the fibre matrix adhesion properties, alkalisation, silane and acetylation treatments on the fibres surface were carried out. Examinations through fourier transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were conducted to investigate the physical and thermal properties of the fibres. Mechanical properties such as flexural and compressive strengths of the sandwich structures made by treated and untreated hemp fibres were studied. Based on the results obtained from the experiments, it was found that the fibre treated with alkalic solution and post-soaked by 8% NaOH exhibited better mechanical strength as compared with other treated and untreated fibre composite samples. Besides, DSC and TGA analysis showed that the thermal stability of all treated fibre was enhanced as compared with untreated samples.