Chitosan hydrogel as a drug delivery carrier to control angiogenesis

An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO₄-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.     

6024例分娩的方式选择与新生儿结局

目的探讨阴道分娩和剖宫产对新生儿的风险。方法对6024例妊娠的分娩方式、剖宫产指征以及新生儿结局回顾性分析。结果剖宫产率为35.3%,其指征主要是头盆不称、社会因素、宫内窘迫、臀位等。分娩新生儿6016例,其中因各种疾患转儿科822例,占13.5%。主要转科原因为早产儿低体重、窒息、高胆红素血症和吸入综合症,各疾病发病率与分娩方式无关。结论剖宫产没有增加新生儿的风险,仍是解决难产的重要手段,但应严格控制手术指征。     

Development of retroviral vectors as safe, targeted gene delivery systems

The transfer of genes of potential therapeutic benefit is presently being attempted in the clinic to treat a number of genetic and virally induced diseases. Many of these protocols use retroviral vectors derived from murine leukemia retroviruses as gene delivery systems. Although these viral delivery systems are well suited for this purpose, a number of their characteristics, some of which are discussed here, are still troublesome. Future retroviral vectors will incorporate nonretroviral features and will be tailored to desired needs for specific uses. These vectors will be safer, more efficient, and targeted in their delivery. Further, expression of the therapeutic genes carried will be limited to the specific target cell type. Some of the recent advances that have been made towards this goal are reviewed here.     

心血管疾病基因治疗进展

载体是基因治疗的一个限速因素。本文主要介绍了近两年来基因运载体系，基因转移方式，新的基因治疗策略的进展以及它们在心血管中的应用。     

透皮给药研究的新进展

透皮给药安全可控，是无创给药的新途径，有着广阔的市场前景。现有的透皮药物限于小分子和低浓度，角质层屏障使大多数药物难以通过或难以达到有效浓度和有效速率。透皮给药的关键在于促进药物渗透，使药物透皮吸收进毛细血管。促渗手段有：使用化学促渗剂；对药物进行化学修饰制成前体药物；使用物理方法；将药物载入载体。这些方法的原理大致分为三种：改变角质层结构；外力驱动药物；将药物进行修饰或包裹。简要地介绍了增强药物透皮的物理方法和载体方法研究的新进展。     

Faster gastric emptying for glucose-polymer and fructose solutions than for glucose in humans

Summary This study examined the rates of gastric emptying for water and 13 different carbohydrate-containing solutions in seven subjects, using conventional gastric intubation techniques. The rates of gastric emptying for water and a 10% glucose-polymer solution were also measured during 90 min of treadmill running at 75% of each subject's maximum oxygen consumption . At rest, 15% glucose-polymer (P) and fructose (F) solutions emptied more rapidly from the stomach and provided a faster rate of carbohydrate delivery than did a 15% glucose (G) solution (p<0.05). The G solutions showed a constant energy delivery rate of 3.3 kcal · min^–1; energy delivery from P and F solutions rose with increasing solution concentrations. The osmolality of the gastric aspirate predicted the rate of gastric emptying for all solutions (p<0.05) but overestimated rates of emptying for 10% and 15% P solutions and underestimated emptying rates for 10% and 15% F solutions. Exercise at 75% decreased the rate of gastric emptying of water but not of 10% P solutions. Thus the different rates of gastric emptying for different carbohydrate-containing solutions were not entirely explained by differences in osmolality. Furthermore, exercise may have different effects on the gastric emptying rates of water and carbohydrate solutions.     

Dexamethasone loaded bioresorbable films used in medical support devices: structure, degradation, crystallinity and drug release

Bioresorbable polymer films containing dexamethasone (DM) were prepared using a solution processing technique. Investigation of the films focused on cumulative DM release as affected by film morphology (drug location/dispersion in the film) and degradation processes. Two film structures were studied: A-type, a polymer film with large drug crystals located on the film’s surface, and B-type, a polymer film with small drug particles and crystals distributed within the bulk. The effect of the polymer’s degree of crystallinity on the drug release profile was also studied. Prototypical applications of these films are biodegradable medical support devices which combine mechanical support with drug release. In most of our studied systems the drug release profile from the film is determined mainly by both drug location/dispersion in the film and the polymer’s weight loss rate. All release profiles from A-type films exhibited a burst effect of approximately 30%, accompanied by a second release phase at a constant rate, whereas the release profiles from B-type films were determined mainly by the degradation profile of the host polymer, and did not exhibit any burst effect. A high degree of crystallinity is important for the current application, since good mechanical properties are required. This contributes to slower drug release rates, mainly at relatively low weight losses, whereas at high weight losses, where a porous structure is created, the crystallinity almost does not affect the rate of drug release. The shape of the porous structure that develops with degradation also affects the drug release profile from the B-type films.     

In Vitro and In Vivo Characterization of MEMS Microneedles

Transdermal drug delivery TDD systems have many advantages but are conventionally limited by the low permeability of skin. The idea of using microneedles to painlessly penetrate the topmost impermeable stratum corneum has previously been put forward. In this paper, the fabrication of solid and hollow silicon microneedles with straight side-walls and with the following dimensions: 20–100 m in diameter and 100–150 m in length is described. In vitro tests demonstrate that with prior solid microneedle application, transdermal drug transport is significantly increased by 10–20 times, with the degree of enhancement being related to needle diameter. In vivo tests in diabetic animals, however, were unable to demonstrate any delivery of insulin through the hollow microneedles. It is proposed that two factors, microneedle length and tip sharpness, have to be improved for systemic drug delivery to be seen in vivo.     

生理参数及药物注射方式对球形实体肿瘤中药物输运的影响

目的　研究球形实体肿瘤中生理参数对药物输运的影响，以及探讨有较好效果的药物注射方式。方法　设肿瘤中毛细血管网成球对称分布，肿瘤中的毛细血管表面积和肿瘤体积之比为半径的函数。肿瘤间质为多孔介质，化学药物透过毛细血管壁进入肿瘤间质，在肿瘤间质中输运满足扩散方程。肿瘤外正常组织富含血管和淋巴，药物能被淋巴管吸收，药物输运采用改进的药代动力学模型。用肿瘤中各部位药物浓度维持在最小药物浓度MEC水平以上的时间曲线面积(AUC)来衡量药物的效果。结果　增大肿瘤间质中毛细血管对药物的通透性P，提高药物在肿瘤间质的扩散系数D，AUC的值均增大。在给出的六种给药方式中，分时段连续滴注和等时间间隔一次性注射的给药方式，它们的AUC值最大。结论　增大肿瘤间质中毛细血管对药物的通透性，提高药物在肿瘤间质的扩散系数，以及采用分时段连续滴注和等时间间隔一次性注射的给药方式，有利于肿瘤的治疗。     

驻极体促进药物透皮吸收的研究进展

近年来，经皮给药的促透方法和技术发展迅速，有关物理学、化学、药剂学的方法和技术的研究都很多。许多新方法和新技术的应用，使经皮给药系统逐渐成为一种成熟的给药方法。本文主要介绍驻极体透皮给药制剂的研究进展及其相关透皮机理。