生物医用高分子材料在药物控释系统中的应用

药物控制释放体系是继传统载药体系发展起来的一种新型的疾病治疗体系。生物医用高分子材料作为药物控释载体的研究逐渐成为热点之一。近年来,随着研究的深入,生物医用高分子材料在药物控释系统中的运用得到了广泛的发展。本文简要介绍了常用天然医用高分子材料如胶原、纤维素以及环糊精和合成医用高分子材料如聚乳酸、聚酸酐等在药物控释系统中的应用,并对这类材料的应用进行了展望。     

γ-聚谷氨酸的微生物合成、相关基因及应用展望

γ-聚谷氨酸是一种具有极强水溶性、生物相容性、可完全降解性的环境友好型新材料。介绍γ-聚谷氨酸的基本性质、微生物合成及其影响因素,综述其合成相关基因、合成酶复合体的研究进展及在水凝胶和药物载体方面的应用前景。     

ε-聚赖氨酸的微生物合成与降解

ε-聚赖氨酸为一种均聚氨基酸,由单个赖氨酸分子在α-羟基和-ε氨基形成酰胺键而连接成的多聚体,目前主要通过白色链霉菌(Streptomyces albulus)的微生物合成进行生产,具有抑菌谱广、热稳定性好、在酸碱条件下稳定等特点,作者综述了ε-聚赖氨酸微生物合成的方法、可能的生物合成和降解机制等,并简要介绍ε-聚赖氨酸作为食品保鲜剂在食品和生物高分子材料在基因治疗、药物载体、基因芯片、高吸水性材料等方面的应用前景。     

海藻酸钠壳聚糖微球作为药物载体的研究进展

海藻酸钠壳聚糖微球是具有生物粘附性且能结合和传递大分子药物的天然高分子材料,且在生物医学领域具有广阔应用前景的药物载体。它具有生物黏附性、生物相容性、生物可降解性、对人体无毒性且能够结合和传递大分子药物的天然高分子材料。海藻酸钠壳聚糖微球作为载药微球具有提高药物的生物利用度、延长药物的作用时间等优点。国内外近些年已将其应用于药剂学领域,以及将其作为药物载体经微球化与药物结合形成给药系统的研究也在逐步开展并取得了较多成果。本文主要阐述海藻酸钠壳聚糖微球的主要生物特性、作用特点及其在医学领域中应用的研究进展,并对其应用前景进行探讨。     

生物合成材料聚β-羟基丁酸(PHB)的研究进展

聚β-羟基丁酸(PHB)是原核微生物在碳、氮营养失衡的情况下,作为碳源和能源贮存在生物体内的一类热塑性聚酯.它作为微生物合成的可降解材料,除了具有与化学合成高分子相似的性质外,还具有一般化学合成高分子没有的性质,如光学活性好、透氧性低、抗紫外线辐射、生物可降解性、生物组织相容性、压电性和抗凝血性等,具有广阔的应用前景,越来越受到人们的关注.国内外的许多公司和科研机构纷纷开展可降解塑料的研发工作.着重介绍了PHB的理化性质、检测方法、生物合成、降解以及基因改良菌种方面的研究进展,同时对其应用、目前存在的问题以及可能的解决方案进行了讨论.     

聚乙二醇-聚乳酸嵌段共聚物在药物递送系统中的应用

聚乙二醇-聚乳酸嵌段共聚物具备良好的生物相容性和生物可降解性,是良好的纳米级药物载体。嵌段共聚物具有载药能力强、粒径小、体内循环时间长、主动靶向性和被动靶向性等特点,因此在药物递送系统中得到广泛应用。简要介绍了聚乙二醇-聚乳酸嵌段共聚物的合成和性质,及其作为脂质体、胶束、微球等载体在药物递送系统中的最新进展。     

聚谷氨酸在医药领域的应用

聚谷氨酸是一种天然的氨基酸聚合物,具有强的水溶性、生物相容性、生物可降解性、无毒等特性,是一种新型绿色环保的生物材料。聚谷氨酸作为药物载体、疫苗佐剂、医用粘合剂和组织工程材料等应用于医药领域时,可表现出更好的生物相容性、更低的生物毒性,可提高药物的靶向性,可有效提高药效,改善药物或材料的性能,因此具有十分广阔的应用前景。本文综述了聚谷氨酸在医药领域的的应用,为下一步的研究和商业化的应用提供参考。     

γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物的制备及其肝靶向性分析

制备一种γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物［Poly (γ-glutamic acid)D-galactose esterifiable derivative-Cisplatin Complex Compound,γ-D+-DDP］,并考察其体内靶向性。通过生物发酵获得大分子γ-聚谷氨酸［Poly (γ-glutamic acid),γ-PGA］,利用酸降解得到可以作为药物载体的小分子γ-聚谷氨酸;利用凝胶色谱柱检验小分子γ-聚谷氨酸的分子量;利用HPLC检测释放的游离顺铂含量,得到复合物在小鼠体内靶向性分布情况;利用HE组织切片染色,观察脏器受损伤情况及靶向分布。实验结果表明：成功获得γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物,该复合物载药率达9.4%~10.2%;HPLC结果表明注射复合物后,肝脏中药物显著增加而肾脏中药物分布明显减少,大大减少了肾毒性,肝靶向作用明显。因此,γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物是一种有效的具有肝靶向性的抗肿瘤药物,具有潜在的临床应用价值;通过生物发酵获得的γ-聚谷氨酸可用于药物载体,赋予药物新的特点。介绍了制备一种γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物[Poly (γ-glutamic acid)-D-galactose esterifiable derivative -Cisplatin Complex Compound,（γ-D+-DDP）],并考察其体内靶向性。通过生物发酵获得大分子γ-聚谷氨酸[Poly (γ-glutamic acid),γ-PGA],利用酸降解得到可以作为药物载体的小分子γ-聚谷氨酸;利用凝胶色谱柱检验小分子γ-聚谷氨酸的分子量;利用HPLC检测释放的游离顺铂含量,得到复合物在小鼠体内靶向性分布情况;利用HE组织切片染色,观察脏器受损伤情况及靶向分布。实验结果表明：成功获得γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物,该复合物载药率达9.4% ~10.2%;HPLC结果表明注射复合物后,肝脏中药物显著增加而肾脏中药物分布明显减少,大大减少了肾毒性,肝靶向作用明显。因此,γ-聚谷氨酸-D-半乳糖酯化衍生物-顺铂复合物是一种有效的具有肝靶向性的抗肿瘤药物,具有潜在的临床应用价值;通过生物发酵获得的γ-聚谷氨酸可用于药物载体,赋予药物新的特点。     

可生物还原聚酰胺胺作为基因递送载体的研究进展

基因治疗是指通过将治疗基因导入特定细胞并调控基因表达,以治疗由基因异常或缺失引起的疾病的一种治疗方法。良好的基因载体将基因高效地载入细胞核后,应能在体内降解,具有良好的生物相容性。可生物还原聚酰胺胺[bio-reductive poly (amido amine), rPAA]不仅具有聚酰胺胺自身具有的溶血活性低、与基因分子结合能力强以及结构与多肽类似等优点,而且在胞外生理条件下稳定,在胞内还原性条件下容易降解、细胞毒性低、效率转染高,因而成为研究热点。本文综述了近十年来含有可生物还原聚酰胺胺作为基因载体的研究进展,其中详细介绍了其合成方法以及基因治疗应用。     

PGS支架的合成、特性及在生物医学中应用的研究进展

聚癸二酸甘油酯(PGS)是一种生物可降解的高分子聚合弹性体,因其良好的性能,在许多生物医学研究中应用广泛。PGS支架的机械性能与机体软组织相似,依从性好,降解时以表面侵蚀的方式降解,不伴有膨胀或变形,周围组织炎症反应、纤维变性轻,与多种细胞相容性好。基于PGS良好的性能,主要应用于软组织替代和软组织工程,比如心肌、血管、神经、软骨、视网膜、鼓膜,另外也有用于药物转运载体、组织粘附材料的研究。     

Animal experiments using mammals are essential to the study on the mechanisms of phenomena produced in the human body in the space environment.

The animal experiments have contributed to the physiology and medicine concerned with the care and cure of patients as well as with an understanding of mechanisms of various diseases and human health. In particular, the numerous mammals have been used for the medical researches. Similarly, to investigate the phenomena in the human body that occur in the space environment, the various mammals have been used for the medical researches in space. Since the human with frontier spirits will never stop continuing the space development and utilization, the space medical and physiological researches using mammals as well as subjects are more important and necessary for the future space activities. The mammal modules in spacecrafts and space station are produced for the rodents at this time. Therefore, from various viewpoints, the rats and mice are the first choice for space mammal experiments of medical or life science researches and space modules for the mammal should be carefully and extensively designed.     

Long-term expression with a cationic polymer derived from a natural polysaccharide: schizophyllan

Among the various synthetic gene carriers based on biomaterials, cationic polymers with polysaccharide backbones have long been studied as nonviral vectors due to their low immunogenicity and high water solubility. Schizophyllan, a beta-(1,3)-glucan, is one of the various polysaccharides that are clinically administered. Furthermore, its safety in the human body has already been confirmed. Various functional groups can be selectively introduced into the side chain, not into the main chain of schizophyllan. Therefore, we have synthesized various oligoamine conjugates from schizophyllan. It was confirmed that their in vitro transfection efficiencies are superior to that of polyethylenimine by adjusting the molecular weight and the degree of amination of cationic schizophyllan. While it was possible to reduce cytotoxicity by adjusting the amount of DNA complex per cell, as seen with poly-L-lysine, polyethylenimine, and chitosan, PEGylation was the most effective means of reducing toxicity. Furthermore, using cationic schizophyllan carriers, it was also possible to express a reporter protein for a long period of time due to a long residence time of plasmid DNA in cells.     

Noninvasive in vivo cell tracking using molecular imaging: A useful tool for developing mesenchymal stem cell-based cancer treatment

Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body. Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes, understanding pathophysiological mechanisms of diseases, and evaluating the kinetics/dynamics of cell therapies. In particular, mesenchymal stem cells (MSCs) have shown promise in recent years as drug carriers for cancer treatment. They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells, and to optimize therapy. The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition, and the exact interactions between MSCs and specific cancer microenvironments are not clear. In this review, a multitude of labeling approaches, imaging modalities, and the merits/demerits of each strategy are outlined. In addition, specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided. Finally, present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.     

Modelling studies to estimate the prevalence of foot-and-mouth disease carriers after reactive vaccination

Foot-and-mouth disease (FMD) is a highly contagious and economically significant viral disease of cloven-hoofed animals. Vaccination can be used to help restrict the spread of the infection, but evidence must be provided to show that the infection has been eradicated in order to regain the FMD-free status. While serological tests have been developed, which can identify animals that have been infected regardless of vaccination status, it is vital to know the probable prevalence of herds with FMD carriers and the within-herd prevalence of those carriers in order to design efficient post-epidemic surveillance strategies that establish freedom from disease. Here, we present the results of a study to model the expected prevalence of carriers after application of emergency vaccination and the impact of this on the sensitivity of test systems for their detection. Results showed that the expected prevalence of carrier-containing herds after reactive vaccination is likely to be very low, approximately 0.2%, and there will only be a small number of carriers, most likely one, in the positive herds. Therefore, sensitivity for carrier detection can be optimized by adopting an individual-based testing regime in which all animals in all vaccinated herds are tested and positive animals rather than herds are culled.     

The economics of evolution: Henry Ford and the Model T

For the past 30 years evolutionary biologists have used a fictional tale about engineer and businessman Henry Ford to help illustrate the undesirability of over-design. Thus, on discovering that kingpins were rarely damaged in scrapped Model T automobiles, Henry Ford is alleged to have concluded that the kingpins were unnecessarily durable and asked that they be built to a cheaper specification. The general lesson that has been drawn from this tale is that natural selection will act to equalize the mortality risks accruing from damage to each part of the organism's body. Yet it is well known, at least as far as humans are concerned, that death is more likely to be attributed to a failure of some organs compared to others. To understand why this might be so, we use some graphical and mathematical models to show that even if all body organs were equally important to survivorship, then the optimal investment solution that maximizes whole-organism longevity will typically not be the solution that equalizes the fail-times of the individual organs. As with natural organisms, the key to any optimal investment policy in multi-component systems is understanding what 'bang you can get for your buck'. Moreover, we use a specific model to show that, even following selection to ameliorate the effects of damage, those body parts that receive more damage are still more likely to be the ultimate cause of death – that is, there is 'under-compensation'. Therefore, the decision to make the kingpins more cheaply should not have been based only on the fact they rarely cause car failure compared to other car components. Such arguments wrongly assume that if one car part (or body part) is less durable than the others, then it will always be the reason for any future breakdown (or death).     

Liposomes as delivery agents for medical imaging

Medical imaging requires an appropriate intensity of signal from the area of interest in order to differentiate certain structures from surrounding tissues, regardless of the modality used. In the majority of cases, contrast agents specific for each imaging modality are necessary to achieve a sufficiently intense signal. To facilitate the accumulation of contrast in the required zone, various microparticulates have been suggested as carriers for contrast agents. Among these carriers, liposomes - microscopic artificial phospholipid vesicles - draw special attention because of their easily controlled properties and useful pharmacological characteristics. This review will discuss how the advantages of liposomes have been used so far in the rapidly growing field of diagnostic medical imaging.     

Receptor-targeted nanocarriers for therapeutic delivery to cancer

Efficient and site-specific delivery of therapeutic drugs is a critical challenge in clinical treatment of cancer. Nano-sized carriers such as liposomes, micelles, and polymeric nanoparticles have been investigated for improving bioavailability and pharmacokinetic properties of therapeutics via various mechanisms, for example, the enhanced permeability and retention (EPR) effect. Further improvement can potentially be achieved by conjugation of targeting ligands onto nanocarriers to achieve selective delivery to the tumour cell or the tumour vasculature. Indeed, receptor-targeted nanocarrier delivery has been shown to improve therapeutic responses both in vitro and in vivo. A variety of ligands have been investigated including folate, transferrin, antibodies, peptides and aptamers. Multiple functionalities can be incorporated into the design of nanoparticles, e.g., to enable imaging and triggered intracellular drug release. In this review, we mainly focus on recent advances on the development of targeted nanocarriers and will introduce novel concepts such as multi-targeting and multi-functional nanoparticles.     

Glycobiology in the field of aging research--introduction to glycogerontology

In populations where demographies are shifting towards increased average age, the importance of gerontology is also increasing. The main purpose of gerontology is to elucidate the mechanisms of deterioration, which occur in various parts of the human body through aging, and use this knowledge to improve quality of life among the elderly. By the elucidation of the human genome, a revolutionary development is expected to occur in the field of medical science in the near future. Many important genes related to the aging processes of various organs have already been found and are expected to be useful in the future development of geriatric medicine. However, most of the proteins produced by the human body contain sugar chains, whose importance as biosignals for multi-cellular organisms was revealed by the recent development of the new field of glycobiology. Since sugar chains are formed as secondary gene products by the concerted action of glycosyltransferases, the structures of sugar chains are less strictly regulated than proteins. Accordingly, most of the biosignals associated with sugar chains are not essential for the maintenance of life itself, but are necessary to maintain the ordered social life of cells constructing multi-cellular organisms. Hence, investigation of structural changes of sugar chains that is caused by aging is expected to produce quite a lot of useful information pertaining to the elucidation of diseases induced by aging. This review will summarize our current knowledge of such changes found in the sugar chains of glycoconjugates resulting from the aging process.     

Carotenoid metabolism: biosynthesis, regulation, and beyond

Carotenoids are Indispensable to plants and play a critical role in human nutrition and health. Significant progress has been made in our understanding of carotenoid metabolism in plants. The biosynthetic pathway has been extensively studied.Nearly all the genes encoding the biosynthetic enzymes have been isolated and characterized from various organisms. In recent years, there is an increasing body of work on the signaling pathways and plastid development, which might provide global control of carotenoid biosynthesis and accumulation. Herein, we will highlight recent progress on the biosynthesis,regulation, and metabolic engineering of carotenoids in plants, as well as the future research towards elucidating the regulatory mechanisms and metabolic network that control carotenoid metabolism.     

Perspectives on the genetic architecture of divergence in body shape in sticklebacks

The body shape of fishes encompasses a number of morphological traits that are intrinsically linked to functional systems and affect various measures of performance, including swimming, feeding, and avoiding predators. Changes in shape can allow a species to exploit a new ecological niche and can lead to ecological speciation. Body shape results from the integration of morphological, behavioral and physiological traits. It has been well established that functional interdependency among traits plays a large role in constraining the evolution of shape, affecting both the speed and the repeated evolution of particular body shapes. However, it is less clear what role genetic or developmental constraints might play in biasing the rate or direction of the evolution of body shape. Here, we suggest that the threespine stickleback (Gasterosteus aculeatus) is a powerful model system in which to address the extent to which genetic or developmental constraints play a role in the evolution of body shape in fishes. We review the existing data that begins to address these issues in sticklebacks and provide suggestions for future areas of research that will be particularly fruitful for illuminating the mechanisms that contribute to the evolution of body shape in fishes.