Controlled synthesis of amphiphilic biodegradable polylactide‐grafted dextran copolymers

The whole controlled synthesis of novel amphiphilic polylactide (PLA)‐grafted dextran copolymers was achieved. The control of the architecture of such biodegradable and potentially biocompatible copolymers has required a three‐step synthesis based on the “grafting from” concept. The first step consisted of the partial silylation of the dextran hydroxyl groups. This protection step was followed by the ring‐opening polymerization of D ,L ‐lactide initiated from the remaining OH functions of the partially silylated polysaccharide. The third step involved the silylether group deprotection under very mild conditions. Based on previous studies, in which the control of the first step was achieved, this study is focused on the last two steps. Experimental conditions were investigated to ensure a controlled polymerization of D ,L ‐lactide, in terms of grafting efficiency, graft length, and transesterification limitation. After polymerization, the final step was studied in order to avoid degradation of both polysaccharide backbone and polyester grafts. The chemical stability of dextran backbone was checked throughout each step of the synthesis. PLA‐grafted dextrans and PLA‐grafted (silylated dextrans) were proved to adopt a core‐shell conformation in various solvents. Furthermore, preliminary experiments on the potential use of these amphiphilic grafted copolymers as liquid/liquid interface stabilizers were performed. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2577–2588, 2004     

Synthesis and characterization of novel thermoresponsive‐co‐biodegradable hydrogels composed of N‐isopropylacrylamide,poly(L‐lactic acid), and dextran

A series of novel multifunctional hydrogels that combined the merits of both thermoresponsive and biodegradable polymeric materials were designed, synthesized, and characterized. The hydrogels were copolymeric networks composed of N‐isopropylacrylamide (NIPAAM) as a thermoresponsive component, poly(L‐lactic acid) (PLLA) as a hydrolytically degradable and hydrophobic component, and dextran as an enzymatically degradable and hydrophilic component. The chemical structures of the hydrogels were characterized by an attenuated total reflection–Fourier transform infrared spectroscopy (ATR–FTIR) technique. The hydrogels were thermoresponsive, showing a lower critical solution temperature (LCST) at approximately 32 °C, and their swelling properties strongly depended on temperature changes, the balance of the hydrophilic/hydrophobic components, and the degradation of the PLLA component. The degradation of the hydrogels caused by hydrolytic cleavage of ester bonds in the PLLA component was faster at 25 °C below the LCST than at 37 °C above the LCST, determined by the ATR–FTIR technique. Due to their multifunctional properties, the designed hydrogels show great potential for biomedical applications, including drug delivery and tissue engineering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5054–5066, 2004     

巯基葡聚糖凝胶分离富集光度法测定镉的研究

研究了在ＴｒｉｔｏｎＸ－１００存在下，新显色剂邻羧基苯基重氮氨基偶氮苯（ＣＤＡＡ）与镉的显色体系，在ｐＨ１０．６的Ｎａ２Ｂ４Ｏ７－ＮａＯＨ体系中，显色反应灵敏度很高。络合物的最大吸收位于５４５ｎｍ处，其摩尔吸光系数为２．２２×１０＾５Ｌ·ｍｏｌ＾－１·ｃｍ＾－１。镉含量在０￣１２μｇ／２５ｍＬ符合比耳定律。将该体系用于巯基葡聚糖凝胶分离富集－光度法测水样中微量镉，结果令人满意。     

Reactive polymeric nanoparticles based on unconventional dextran derivatives

Unconventional dextran derivatives with reactive tosyl- and deoxy-azido moieties were synthesized homogeneously under various reaction conditions. Well soluble tosyl dextran of a high degree of substitution up to 1.66 was prepared applying N,N-dimethylacetamide/LiCl as solvent. Almost 50% of secondary toslyate moieties could be replaced by nucleophilic displacement reaction with azide ions. The structure of the products was efficiently analyzed by NMR spectroscopy also after peracylation of the unconventional dextran derivatives. Applying a simple dialysis technique, nanospheres with a size in the range from 160 to 420 nm (D50%) were obtained that possess reactive functional tosyl- and deoxy-azido groups.     

Synthesis and in vitro degradation of poly(N‐vinyl‐2‐pyrrolidone)‐based graft copolymers for biomedical applications

This work is devoted to the design of a novel family of hydrosoluble biomaterials: poly(N‐vinyl‐2‐pyrrolidone) (PVP)‐based graft copolymers. A synthesis route has been elaborated in which ω‐functionalized PVP is prepared via chain‐transfer radical polymerization, end‐group modified, and subsequently grafted onto a polyhydroxylated backbone, typically dextran or poly(vinyl alcohol). The resulting graft copolymer biomaterials are designed for use in various biomedical applications, particularly as materials with a stronger potential for plasma expansion than already existing products have. The graft copolymers are potentially degradable because the PVP grafts are connected to the polyol backbone via a hydrolytically labile carbonate or ester linkage. The degradation of the graft copolymers was performed in vitro over a period of 6 weeks. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3652–3661, 2002     

Determination of the swelling behavior of superabsorbent polymers by a tracer-assisted on-line spectroscopic measurement

This work reports on a method for the accurate determination of kinetic swelling behavior and properties of superabsorbent polymers by a tracer-assisted on-line spectroscopic measurement. Based on monitoring the spectral absorption of a tracer compound (blue dextran 2000) at 610 nm in a superabsorbent polymer containing solution, the swelling (water absorption) of the polymer during the process can be followed, from which the parameters in a kinetic equation can be obtained. The results showed that the data obtained by the present method has a good measurement precision and accuracy, in which the relative differences were less than 4.0% when comparing the data measured by a reference method (i.e., the tea bag method). Since the present method can perform an on-line measurement, it is much superior to the current tea bag method and therefore is very suitable to be used in the process related study for the swelling behavior of superabsorbent polymers in many applications.     

Effect of Molecular Crowding on the Temperature–Pressure Stability Diagram of Ribonuclease A

FT‐IR spectroscopic and thermodynamic measurements were designed to explore the effect of a macromolecular crowder, dextran, on the temperature and pressure‐dependent phase diagram of the protein Ribonuclease A (RNase A), and we compare the experimental data with approximate theoretical predictions based on configuration entropy. Exploring the crowding effect on the pressure‐induced unfolding of proteins provides insight in protein stability and folding under cell‐like dense conditions, since pressure is a fundamental thermodynamic variable linked to molecular volume. Moreover, these studies are of relevance for understanding protein stability in deep‐sea organisms, which have to cope with pressures in the kbar range. We found that not only temperature‐induced equilibrium unfolding of RNase A, but also unfolding induced by pressure is markedly prohibited in the crowded dextran solutions, suggesting that crowded environments such as those found intracellularly, will also oppress high‐pressure protein unfolding. The FT‐IR spectroscopic measurements revealed a marked increase in unfolding pressure of 2 kbar in the presence of 30 wt % dextran. Whereas the structural changes upon thermal unfolding of the protein are not significantly influenced in the presence of the crowding agent, through stabilization by dextran the pressure‐unfolded state of the protein retains more ordered secondary structure elements, which seems to be a manifestation of the entropic destabilization of the unfolded state by crowding.     

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery**

Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.     

A Molecular Study of Aspirin and Tenofovir Using Gold/Dextran Nanocomposites and Surface-Enhanced Raman Spectroscopy

In this study, we show how surface enhanced Raman spectroscopy (SERS) can be used to monitor the molecular behaviour of aspirin and tenofovir as a means of screening medication for quality control purposes. Gold-coated slides combined with gold/dextran nanoaggregates were used to provide signal enhancement of the drugs using SERS. Aspirin (10% w/v) and tenofovir (20% v/v) were analysed in the presence of the nanomaterials to determine trends in molecular response to changes in gold/dextran concentrations. Qualitative analysis of the functional groups showed specific trends where the peak area increased with polarizability, electron density and decreased atomic radii. Steric hinderance effects also affected the trends in peak area due to the amount of gold/dextran nanoparticles in solution. Statistical analysis provided accurate and precise linear relationships (R² = 0.99) for the ester and adenine functional groups of aspirin and tenofovir, respectively. From the above findings, the combined use of gold nano-scaffolds and gold/dextran nanomaterials amplified the Raman signal from the drugs to allow for systematic evaluation of their molecular properties. Although more experiments to correlate the findings are still needed, this SERS approach shows great potential as a screening method in the quality control of medications.     

Capillary electrophoresis-mass spectrometry of intact basic proteins using Polybrene-dextran sulfate-Polybrene-coated capillaries: System optimization and performance

A capillary electrophoresis-mass spectrometry (CE-MS) method using sheath liquid electrospray ionization interfacing was studied and optimized for the analysis of intact basic proteins. To prevent protein adsorption, capillaries with a noncovalent positively charged coating were utilized. Capillaries were coated by subsequent rinsing with solutions of Polybrene, dextran sulfate and Polybrene. The coating proved to be fully compatible with MS detection, causing no background signals and ionization suppression. The composition of the sheath liquid and BGE was optimized using the model proteins α-chymotrypsinogen A, ribonuclease A, lysozyme and cytochrome c. A sheath liquid of isopropanol-water-acetic acid (75:25:0.1, v/v/v) at 2 μL min⁻¹ resulted in optimal signal intensities for most proteins, but caused dissociation of the heme group of cytochrome c. Optimum protein responses were obtained with a BGE of 50 mM acetic acid (pH 3.0), which allowed a baseline separation of the test protein mixture. Several minor impurities present in the mixture could be detected and provisionally identified using accurate mass and a protein modification database. The selectivity of the CE-MS system was investigated by the analysis of acetylated lysozyme. Eight highly related species, identified as non-acetylated lysozyme and lysozyme acetylated in various degrees, could be distinguished. The CE-MS system showed good reproducibility yielding interday (three weeks period) RSDs for migration time and peak area within 2% and 10%, respectively. With the CE-MS system, determination coefficients (R²) for protein concentration and peak area were higher than 0.996, whereas detection limits were between 11 and 19 nM.