ADJUVANTS--TYROSINE DERIVATIVES AND CONTROLLED RELEASE

佐剂--酪氨酸衍生物及其控释

• 批准号: 3546906
• 负责人: ROBERT Samuel LANGER
• 金额: $ 16.14万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3546906
• 关键词: adsorption; antiAIDS agent; antibody formation; biotransformation; calorimetry; chemical synthesis; dosage forms; drug delivery systems; enzyme linked immunosorbent assay; high performance liquid chromatography; immunization; immunoconjugates; immunomodulators; laboratory mouse; mathematical model; mechanical stress; molecular weight; polymers; surface property; synthetic antigens; synthetic peptide; tyrosine analog

The controlled release of marcomolecules from inert polymeric martix devices has been extensively researched by our group. Furthermore, a recently synthesized class of bioerodible polymers, made from the non-peptide linking of typrosine dipeptide derivatives, demonstrates adjuvanticity in both monomeric and polymeric form. The aim of the proposed research is to develop a controlled release immunization implant which will have a two-fold effect. First, the device will produce sustained, controlled release of antigen in vivo, thereby initiating production of antibody specific for that antigen and successfully immunizing the animal. Second, the products formed during polymer hydrolysis will have an adjuvant effect on the immune response, thus enhancing the level and duration of antibody production and improving protection against subsequent challenge. To achieve this goal: 1) Poly(iminocarbonates) composed of N- and C-blocked derivatives of N-(L-tyrosyl)-L-tyrosine will be synthesized and characterized with regard to molecular weight mechanical properties, surface properties, and degradation behavior; 2) The release of model antigens from devices composed of these polymers will be measured and mathematically modelled; 3) Adsorption-desorption studies of polymer and antigen will be conducted to investigate the "depot" effect mechanism of adjuvanticity; 4) Polymeric devices containing antigen and polymer-antigen adsorbates will be implanted or injected in mice, and the antigen- specific antibody levels will be measured by ELISA; and 5) Release patterns from devices will be altered with ultrasound or formulation parameters to determine the effect of dosage on adjuvanticity.

Marcomolecules从惰性聚合物中受控释放 Martix设备已由我们的小组进行了广泛的研究。 此外，最近合成的生物剂类 聚合物，由Typrosine的非肽连接制成 二肽衍生物在两者中都证明了辅助性 单体和聚合物形式。 提议的目的 研究是开发受控释放免疫植入物 它将具有两个倍效应。 首先，该设备将产生 持续的，受控的抗原在体内释放，从而启动 对该抗原的特异性抗体产生并成功地产生 免疫动物。 其次，在期间形成的产品 聚合物水解将对免疫产生辅助作用 响应，从而增强抗体的水平和持续时间 生产和改善对随后挑战的保护。 为了实现这一目标： 1）由N-和C-Blocked组成 N-（L-酪蛋白）-L-酪氨酸的衍生物将合成，并 关于分子量机械的特征 性质，表面特性和降解行为； 2）从这些设备中释放模型抗原 将测量和数学建模聚合物； 3）聚合物和抗原的吸附 - 吸附研究将是 进行调查的“仓库”效应机制 辅助性； 4）含有抗原和聚合物抗原的聚合物设备 吸附物将被植入或注入小鼠，抗原 - 特异性抗体水平将由ELISA测量；和 5）超声将更改设备的释放模式 或制定参数以确定剂量对 辅助性。