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Delivery Systems for Biomolecules, From Biologic Pathway to Chemical Design

机译:从生物途径到化学设计的生物分子输送系统

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Purpose: To demonstrate the feasibility of three rationally designed synthetic systems for sustainedrelease delivery of native proteins, efficient transdermal delivery of polypeptides, and responsive carrier system for delivery of nucleotides. Methods: For protein sustained-release, an aqueous-aqueous "emulsion" was used to load proteins in dextran fine particles without contacting with water-oil or waterair interfaces prior to microencapsulation into PLGA microsphaeres. For transdermal delivery of polvpeptides. a phase-transition microneedle patch was developed, by which lipophobic drugs pre-loaded in the microneedles was released to the dermis layer by swelling of the needle tips. For nucleotides carriers, an endogenous gene condenser, spermine, was polymerized via a pH-responsive degradable linkage. Results: Proteins protected in the dextran microenvironment were released from PLGA microspheres in native form with minimal initial burst. Insulin was released transdermaly from the swollen microneedles without depositing the needle tip materials. The pHresponsive polyspermine showed improved gene silencing activity without causing cytotoxicity. Conclusion: Some long-standing hurdles in developing synthetic delivery systems may best be addressed by rational design on the basis of understanding of biological pathways.
机译:目的:证明三种合理设计的合成系统用于天然蛋白的缓释递送,多肽的有效透皮递送以及用于递送核苷酸的响应性载体系统的可行性。方法:为了蛋白质的持续释放,在微囊化成PLGA微球之前,使用水-水性“乳剂”将蛋白质加载到葡聚糖微粒中,而不与水-油或水-空气界面接触。用于多肽的透皮递送。开发了一种相变微针贴剂,通过预充在微针中的疏脂药物通过针尖的膨胀释放到真皮层。对于核苷酸载体,通过pH响应性可降解键聚合内源基因精胺精胺。结果:在葡聚糖微环境中受保护的蛋白质以天然形式从PLGA微球中释放出来,初始爆发极少。胰岛素从肿胀的微针经皮释放,而没有沉积针尖材料。 pH响应的多精胺显示出改善的基因沉默活性,而不会引起细胞毒性。结论:在理解生物途径的基础上,合理设计可以最好地解决发展合成递送系统中的一些长期障碍。

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