DRUG AND GENE DELIVERY USING POLYMERS AND LIPOSOMES

使用聚合物和脂质体进行药物和基因递送

• 批准号: 8169718
• 负责人: FRANCIS C. SZOKA
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169718
• 关键词: Adjuvant; Cell Nucleus; Cells; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Cytoplasm; Drug Delivery Systems; Endosomes; Environment; Funding; Gene Delivery; Genes; Goals; Grant; Human; Institution; Lipids; Liposomes; Location; Lysosomes; Malignant Neoplasms; Membrane Fusion; Modification; Molecular Motors; Peptides; Pharmaceutical Preparations; Polymers; Prodrugs; Research; Research Personnel; Resources; Source; Surface; United States National Institutes of Health; Vaccines; design; improved; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this research is to use peptides, polymers or liposomes to deliver their contents into the cytoplasm of cells, to characterize the mechanism of delivery and to exploit the low pH environment of the endosome or lysosome to catalyze delivery of polymer/liposomal contents into cytoplasm. Another goal of this research is to develop gene and drug approaches to treat cancer. A third goal of our research is to develop improved adjuvants to use in human vaccines. One approach is to synthesize novel peptide lipids or peptide polymers that can undergo a low pH induced conformational change that results in the exposure of hydrophobic sequences that initiate membrane fusion. The peptide would be attached to the surface of the polymer or liposome in this application. A second approach is to synthesize prodrugs that can undergo either a pH dependent or enzymatic modification which permits their efflux from the lysosomal compartment. In either of these applications chemical and physical approaches are being used to design more efficient drug delivery systems and to determine the limitations to their use. We are also developing peptides that can attach to cellular molecular motors to direct the drug or gene to particular locations such as the nucleus in the cell.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 本研究的目标是利用肽、聚合物或脂质体将其内容物递送至细胞的细胞质中，表征递送机制并利用内体或溶酶体的低pH环境来催化聚合物/脂质体内容物递送至细胞质中。细胞质。 这项研究的另一个目标是开发治疗癌症的基因和药物方法。我们研究的第三个目标是开发用于人类疫苗的改进佐剂。一种方法是合成新型肽脂质或肽聚合物，它们可以经历低pH诱导的构象变化，导致疏水序列暴露，从而引发膜融合。 在本申请中，肽将附着至聚合物或脂质体的表面。 第二种方法是合成可以经历 pH 依赖性或酶促修饰的前药，从而允许它们从溶酶体室中流出。 在这些应用中，化学和物理方法都被用来设计更有效的药物输送系统并确定其使用的限制。我们还在开发可以附着在细胞分子马达上的肽，以将药物或基因引导至特定位置，例如细胞中的细胞核。