Sustained release of a model water-soluble compound via dry powder aerosolizable acetalated dextran microparticles

Objective: To design and characterize aerosol microparticles (MP) to provide sustained release of the water-soluble compound sulforhodamine B (SRB) and achieve effective aerosol dispersion.

Significance: Modulating the release of water-soluble compounds remains a challenge in pulmonary drug delivery.

Methods: SRB and water made up an aqueous solution, while acetalated dextran (Ac-Dex) and isopropyl alcohol made up an organic solution. The two solutions were mixed together, and the solution was spray dried to produce MP. MP were characterized for morphology, size, release kinetics, aerosol dispersion, and cellular interactions.

Results: Ac-Dex MP exhibited corrugated morphology and aerodynamic diameters from 2.06 to 2.86?μm. MP deposited in all stages of a Next Generation Impactor, with >90% fine particle fraction. MP exhibited encapsulation efficiencies >129% with SRB loading values up to 16.7?μg SRB/mg MP. MP exhibited sustained release of SRB at pH 7 and fast release at pH 5. In vitro experiments showed minimal cytotoxicity, successful uptake of MP in epithelial cells, and no disruption to the integrity of epithelial monolayers.

Conclusions: Ac-Dex MP systems demonstrated the ability to provide sustained the release of a water-soluble therapeutic in addition to effective aerosol dispersion for pulmonary applications.     

Grafted poly(ethylene oxide) brushes as nonfouling surface coatings

The identification of design criteria for the prevention of surface fouling by protein adsorption has been an elusive research goal. The current ideas in this domain assume two different directions. One focuses on correlating protein adsorption with macroscopic surface properties such as the water wettability. The second approach involves tailoring the molecular interactions between the adsorbing proteins and the surface. In this paper, we focus on the experimental results and theoretical ideas concerned with tuning the interfacial forces by means of terminally grafted PEO chains.     

Water-soluble trioxanes as potent and safe antimalarial agents

A series of synthetic C-3-aryl and C-12-benzyloxy 1,2,4-trioxane analogues is reported by Posner and co-workers to possess potent antimalarial activity versus Plasmodium falciparum in vitro and versus Plasmodium berghei in vivo in the mouse model of malaria. Several carboxylic acid containing derivatives within these two classes were shown to be superior to the semi-synthetic artemisinin derivative artelinic acid. In addition, one of the compounds claimed is not only more potent than artelinic acid in vivo but also has significantly higher water solubility and lower toxicity. On the basis of these encouraging results, these new, water-soluble peroxide analogues represent useful leads for further drug development.     

Improving Relative Bioavailability of Dicumarol by Reducing Particle Size and Adding the Adhesive Poly(Fumaric-Co-Sebacic) Anhydride

Purpose. This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol. Methods. Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique.Results. In vitro results showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres. In vivo, relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged T_max and decreased C_max in both species. Conclusion. This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.     

喇咕来源水溶性壳聚糖抗肿瘤作用及其免疫调节活性研究

目的从喇咕中提取制备水溶性壳聚糖 ,并研究其抗肿瘤作用及免疫活性。方法按 2 0 0mg (kg·d)剂量灌胃给药 ,观察其对荷瘤小鼠的抑瘤作用和免疫学指标。结果水溶性壳聚糖对S180 和艾氏腹水癌的抑瘤率分别为 58.6%和 54.85% ,与环磷酰胺伍用 ,能增强荷瘤小鼠抑瘤率 ;并能拮抗环磷酰胺所致的副作用。结论喇咕来源水溶性壳聚糖对荷瘤小鼠有显著的抗肿瘤作用 ,并能调节机体免疫功能 ,降低化疗药物的毒副作用。     

水溶性维生素安全性的临床研究(综述)

随着膳食补充剂的发展及临床上水溶性维生素的大量使用，过量摄取水溶性维生素对机体可能产生的毒副作用日益受到重视。本文综述了关于水溶性维生素安全性的一些重要临床研究报道，以及根据现有研究结果初步制定的安全上限水平。     

板蓝根水溶性化学成分的研究

目的:提取、分离、鉴定板蓝根水溶性化学成分。方法:板蓝根水提取液上HP-20大孔吸附树脂,不同浓度乙醇梯度洗脱,洗脱部分经硅胶、凝胶、反相硅胶柱色谱反复分离、纯化,利用波谱技术确定化合物的结构。结果:从板蓝根水提取液中分离得到6个化合物,分别鉴定为(+)-异落叶松树脂醇(1)、落叶松树脂醇-4-O-β-D-吡喃型葡萄糖苷(2)、落叶松树脂醇-4,4′-二-O-β-D-吡喃型葡萄糖苷(3)、表告依春(4)、吲哚-3-乙腈-6-O-β-D-葡萄糖苷(5)、4-羟基-3-吲哚醛(6)。结论:化合物(6)为首次从该植物中分离得到。     

Combined Freeze-Thaw and Chloride Attack Resistance of Concrete Made with Recycled Brick-Concrete Aggregate

The objective of this study was to investigate the physico-chemical properties of concrete made with recycled brick-concrete aggregate, which was the mixture from waste concrete and waste clay brick in a 7:3 ratio. Specifically, this paper investigated the mechanical properties, freeze-thaw resistance, and distribution of water-soluble chloride ions of concrete containing RBCA and fly ash (FA) against combined freeze-thaw and sodium chloride attack. Concrete containing RBCA replacement of natural coarse aggregate and fly ash replacement of Portland cement was subjected to 45 freeze-thaw cycles containing sodium chloride solution. It was discovered that the mechanical properties and freeze-thaw resistance to sodium chloride attack gradually decreased with increasing RBCA content. At the same time, a replacement level of 15% FA by weight resulted in significant improvements in compressive strength and resistance to combined freeze-thaw and chloride attack. Furthermore, using a replacement of 30% FA by weight markedly improved the resistance to chloride ion penetration of concrete due to the lowest water-soluble chloride content.     

香烟烟雾水溶物对人外周血淋巴细胞SCE的影响

SCE频率分析是研究环境诱变剂和致癌剂引起人类遗传物质损伤的有效手段。本文以人外周血淋巴细胞姐妹染色单体交换(SCE)为指标,研究了香烟烟雾水溶物对体外培养的人外周血淋巴细胞SCE的影响。结果表明香烟烟雾水溶物引起人的外周血淋巴细胞SCE数的增加,证明香烟烟雾水溶物具有诱发突变作用。     

Polyanhydride Mierospheres that Display Near-Constant Release of Water-Soluble Model Drug Compounds

A new method to prepare polyanhydride microspheres capable of near-constant sustained release of low molecular weight, water-soluble molecules is presented. The polyanhydrides used were poly-(fatty acid dimer) (PFAD), poly(sebacic acid) (PSA), and their co-polymers [P(FAD-SA)]. Acid orange 63 (AO), acid red 8 (AR), and p-nitroaniline, were used as model release molecules. P(FAD-SA) microspheres containing the molecules with or without gelatin were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 50–125 µm and encapsulated more than 85% of the molecule, irrespective of the compound used. Near-zero-order degradation kinetics were observed for 5 days as judged by sebacic acid (SA) release. Microsphere degradation was pH sensitive, being enhanced at high pH, and became more stable in acidic conditions, irrespective of the incorporation of gelatin in the matrix. For the gelatin-free microspheres, a close correlation of SA release and AO release was observed (2% loading), suggesting a release mechanism that was controlled dominantly by degradation. However, the incorporation of gelatin into the microsphere significantly extended the periods of molecule release from P(FAD-SA) microspheres, although the degradation profile of the microspheres themselves was quite similar to that of gelatin-free microspheres. It is possible that an interaction between FAD monomers and gelatin molecules causes continued release, even after the polymer matrix completely degrades (even after complete degradation, FAD monomers remain because of their poor water solubility). Thermal analysis of polyanhydride microspheres at different degradation stages demonstrated that a crystalline structure was formed between gelatin and the FAD monomers produced with microsphere degradation. This gelatin effect on the extended period of drug release was not observed for microspheres prepared from other polyanhydrides: poly (sebacic acid) and its co-polymer of bis(p-carboxyphenoxy) propane and sebacic acid. It is therefore likely that the crystalline structure formed between gelatin and FAD monomers may function as a reservoir for water-soluble drugs, leading to an extended period of molecule release from the gelatin-loaded P(FAD-SA) microspheres.