柚皮素胃漂浮微丸研究

目的:结合固体分散技术制备柚皮素的海藻酸钙胃漂浮微丸,考察其漂浮率、包封率及体外释放。方法:以Eudragit RLPO为载体材料制备柚皮素固体分散体,粉碎后分散于添加制泡剂的海藻酸钠溶液中,并缓慢滴入添加醋酸的壳聚糖-氯化钙溶液中反应固化,干燥后得到胃漂浮缓释微丸。考察固体分散体对微丸体外释药的影响。结果:成功制备了柚皮素胃漂浮微丸,其在人工胃液中9 h漂浮率大于70%,包封率70%～80%。9 h释放柚皮素65%～70%。结论:运用固体分散技术提高了柚皮素的海藻酸钙胃漂浮微丸在人工胃液中的释放,为多单元胃漂浮给药系统发展提供了思路。     

生物黏附性三七总皂苷-白及多糖-海藻酸钠复合微球的制备及表征

目的利用白及多糖(BSP)的生物黏附性,与海藻酸钠(SA)混合作为复合载体,以具有缓释特性的三七总皂苷(PNS)分散体作为包封药物,制备具有生物黏附性的PNS-BSP-SA复合微球。方法采用离子交联法制备微球,通过单因素试验和正交设计考察并优化处方工艺。通过扫描电镜(SEM)、粒径分布、差示扫描量热法(DSC)分析、溶胀性能测定、体外黏附性能评价、体外释放研究对微球进行表征。结果 PNS-BSP-SA复合微球圆整度较好,表面粗糙不平有褶皱,粒径分布较窄,PNS原料药以无定形状态均匀分散于微球中。最佳处方工艺制备的微球工艺稳定,重现性较好,与直接加入PNS原料药制备的微球相比,PNS分散体微球的载药量、包封率和得率均明显增加,分别为10.34%、51.25%、82.21%,而PNS原料药微球的载药量、包封率、得率分别为4.04%、12.16%、61.35%。BSP的加入增加了SA微球的溶胀性能,明显增加了其在大鼠胃部的滞留率。PNS-BSP-SA复合微球中人参皂苷Rg1的释放较PNS原料药缓慢。结论 BSP增加了微球的生物黏附性,将PNS制备为分散体,提高了微球的载药量、包封率和得率,并使微球具有一定的缓释性能。     

复合膳食纤维对大鼠体内脂质过氧化作用的影响

制备复合膳食纤维 (dietaryfiber,DF) ,并分别探讨复合、混合及三种单一的DF对高脂血症大鼠体内脂质过氧化作用的影响。选健康、断乳Wistar大鼠 6 4只 ,按体重随机分为 8组 ,用高脂饲料诱发高脂血症的同时 ,分别添加 10 %的DF :纤维素 (B组 )、果胶 (C组 )、海藻酸钠 (D组 )、纤维素 -果胶复合物 (E组 )、纤维素 -海藻酸钠复合物 (F组 )、纤维素 -果胶混合物 (G组 )、纤维素 -海藻酸钠混合物 (H组 ) ,以单纯的高脂饲料组为对照组 (A组 ) ,观察各种DF对大鼠的生长发育及脂质过氧化作用的影响。结果显示 :1、添加 10 %的各种DF不影响大鼠的生长发育。 2、各种DF皆可显著升高血清超氧化物歧化酶 (SOD) (P <0 0 1)、谷胱甘肽过氧化物酶 (GSH Px)活性 (P <0 0 1) ,降低丙二醛 (MDA)水平 (P <0 0 5 ,B、D组除外 ) ,提高红细胞膜的流动性 (P <0 0 5 ) ,以复合物、混合物效果为明显。 3、各种DF可不同程度地增加粪重和粪脂排出量 (P <0 0 5 ,D组除外 ) ,以复合物、混合物为明显。提示各种DF皆可不同程度地降低大鼠体内脂质过氧化作用 ,提高红细胞膜的流动性 ,其中可溶性DF效果优于不可溶性DF ,而复合、混合DF的效果又优于单一的DF ,且以复合物效果为佳     

铜绿假单胞菌褐藻胶合成抑制剂筛选模型的建立

目的 建立以铜绿假单胞菌（Pseudomonas aeruginosa）乙酰化褐藻胶的合成为靶向的筛选模型,用于筛选抑制铜绿假单胞菌褐藻胶合成的活性分子。 方法 分别建立铜绿假单胞菌双层平板筛选模型和PalgD-GFP 荧光分子模型,从海洋微生物代谢产物中筛选抑制铜绿假单胞菌乙酰化褐藻胶合成的活性分子。 结果 利用2个筛选模型筛选300余种化合物,获得2种抑制铜绿假单胞菌合成褐藻胶的化合物,且化合物的抑制作用具有浓度依赖性,验证了模型的可行性和有效性。 结论 2种模型结合,可以高效、准确地筛选目标化合物,为解决细菌耐药问题提供了1种有效的手段。     

Urease loaded alginate microspheres for blood purification

In this paper a device, based on urease-loaded microspheres, is presented. The first task of this work was the optimization of a procedure for the alginate microspheres realization, having a radius as close as possible to the optimal one necessary to achieve the maximum enzyme exploitation. This optimal radius was calculated theoretically through a mathematical model which describes the concentration of substrate (urea) inside the microspheres on the assumption of a diffusion-reaction mechanism. The enzyme-loaded microspheres were successfully tested in a prototypal device aimed at the depletion of urea from a circulating fluid simulating blood flow: the results showed that urea concentration in the circulating fluid drops down to less than 25% of the initial value after 5 h.     

Two-level delivery systems based on CaCO3 cores for oral administration of therapeutic peptides

Abstract

Two-level systems for oral delivery of therapeutic peptides were developed; the carriers consist of CaCO₃ cores included into alginate granules. Such systems were first used for the delivery of low molecular weight drugs. It was shown that efficiency of encapsulation of peptides depends on their pI value, hydrophobicity, characteristics of the compounds used for doping CaCO₃ cores, their surface potential and the techniques employed for loading peptides into the first-level carriers. Doping CaCO₃ cores with dextran sulphate save their viability compared to the pristine CaCO₃ cores, but ensures delivery of the desired quantity of peptide when using a smaller amount of delivery systems. Introducing the inhibitor of peptidases leads to an increase in the concentration of peptide in rat blood after intragastric administration of the developed delivery systems. Scanning electron microscopy and energy-dispersive X-ray spectroscopy demonstrated the presence of fragments of destructed first-level carriers in blood and plasma of experimental animals.     

盐酸莫西沙星静电纺丝膜的制备及性能研究

目的:制备具有抗菌作用的盐酸莫西沙星(MH)静电纺丝膜。方法:以聚乙烯醇(PVA)和海藻酸钠(SA)为载体,MH为模型药物,制备具有优良透气性能的抗菌静电纺丝膜。以溶液可纺性、静电纺丝的形态结构等为指标,筛选12%PVA与2%SA不同体积比(4:1、3.5:1.5、3:2、2.5:2.5、2:3、1:4)的纺丝溶液及静电纺丝膜的加药量以确定最佳处方。测定静电纺丝膜的透气性能并与口罩无纺布比较。结果:最佳处方为12%PVA与2%SA的体积比为3:2,加药量为2%;纺丝溶液可纺性好,所制静电纺丝直径小且均匀,表面光滑,串珠状纺丝少,收率为(86.73±2.92)%,透气性能优于无纺布(P<0.05)。结论:制备的MH静电纺丝膜载药均匀,具有良好的透气性能。     

Composite alginate microspheres as the next-generation egg-box carriers for biomacromolecules delivery

Introduction: Alginate microspheres are versatile tools for the delivery of a wide range of therapeutic biomacromolecules. This naturally occurring biopolymer has many unique properties making it an ideal candidate for tailoring with different composites of polymers leading to the formation of strong complexes for a broad range of applications.

Areas covered: This article overviews various types of composite alginate microspheres, methods of preparation, new technologies available, physico-chemical characteristics, controlled release profiles, applications and the future directions of composite alginate microsphere delivery system for biomacromolecules.

Expert opinion: Composite alginate microsphere systems are the ideal carriers for controlled delivery applications because of their ability to encapsulate a myriad of therapeutic drugs, proteins, enzymes, DNA, antisense oligonucleotides, vaccines, growth factors and chemokines as well as the ease of processing, mechanical properties, biocompatibility, high bioavailability, controlled release rates, stability, suitability for different administration modes, targeted/localized delivery of different agents and large-scale production with cost-effectiveness. This article presents updated information of applying microalginate-based technologies and tools in the biomedical field which will benefit research scientists and clinical physicians or biopharmaceutical industries keen in the development of application-based new therapeutic and diagnostic strategies for various diseases. Furthermore, this technology will play more important roles in biosensors, vaccination, tissue engineering, cancer chemotherapeutics and stem cell research.     

Drug delivery strategies using polysaccharidic gels

Hydrogels are hydrophilic polymeric networks, with chemical or physical crosslinks, that are capable of swell and can retain a large amount of water. Among the numerous types of macromolecules that can be used for hydrogel formation, polysaccharides show very attractive advantages in comparison to synthetic polymers. They are widely present in living organisms, are usually abundant and show a number of peculiar physicochemical properties; furthermore, these macromolecules are, in most cases, non-toxic, biocompatible and can be obtained from renewable sources. For these reasons, polysaccharides seem to be particularly suitable for different applications in the wide field of pharmaceutics. As examples of the studies that have been carried out on this topic, this review will focus on two polysaccharides, alginate and xyloglucan. Alginate has been, and still is, extensively investigated and has numerous industrial applications, whereas xyloglucan was chosen because, although it has been much less studied, it shows interesting properties that should find important practical uses in the near future. The possible advantages of physical gels over those that are chemically crosslinked are also discussed.     

Pharmacokinetics and analgesic effect of ketorolac floating delivery system

Abstract

Objectives: The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form.

Methods: KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay.

Results: The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8?h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the C_max (2.2?±?0.3?µg/ml) was achieved at ～2?h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets.

Conclusion: KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.