CONTROLLED RELEASE OF ATRIAL NATRIURETIC FACTOR

心房钠尿因子的受控释放

基本信息

  • 批准号:
    6388410
  • 负责人:
  • 金额:
    $ 12.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1997
  • 资助国家:
    美国
  • 起止时间:
    1997-04-04 至 2003-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Adapted from applicant's abstract) The long-term research objectives of this proposal are the formulation and synthesis of biodegradable polymeric matrices which can incorporate and stabilize macromolecules (MW>1000) and release them in a controlled fashion as bioactive agents for up to 1 month. Macromolecules, such as peptides and proteins, are becoming increasingly important for use in biopharmaceutical research and as potential therapeutic agents. However, their complex three-dimensional structures and large size generally results in easy inactivation, poor oral bioavailability and rapid metabolism, limiting their use to short-term parenteral settings. Controlled release polymer systems potentially offer many advantages which may overcome these obstacles. For example, protection during storage and delivery, maintenance of drug levels without peaks and troughs, reduced dosages, increased dosing intervals, localized delivery, and improved patient comfort and compliance. Delivery systems for low molecular weight molecules are being widely used both experimentally, to study chemotactic agents, cell extracts and others, and clinically, to treat prostate cancer using Lupron Depot or deliver contraceptives using Norplant. In spite of these advances, no clinically available controlled release system for large molecular weight compounds exists. This is because of both formulation (polymer) and stability (protein) issues. The candidate's hypothesis is that biodegradable controlled release polymers can be developed for the long-term delivery of bioactive macromolecules, such as peptides and proteins, at efficacious levels. She has chosen PLGA [poly(lactide-co-glycolide)], a biodegradable copolymer with FDA approval for biomedical application, as a release matrix. Atrial natriuretic peptide (ANP), a 3000 MW molecule with therapeutic potential in hypertension and congestive heart failure, will serve as a model compound. The hypothesis will be tested through the following specific aims. 1) To design a biodegradable controlled release system by optimizing the performance properties of PLGA for the delivery of ANP over one month, and study the role of polymer erosion in drug delivery using both theoretical and experimental approaches; 2) To examine protein stability as it relates to PLGA preparation, storage, and release and develop strategies to preserve ANP bioactivity: 3) To evaluate the pharmacokinetics of the PLGA delivery system and the efficacy of the controlled release form of ANP using cell culture and animal model bioassays. The candidate states her belief that the successful completion of these objectives will greatly facilitate, first the investigations, and ultimately, the clinical applications of large, bioactive protein macromolecules. (End of Abstract)
描述

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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MARIA A RUPNICK其他文献

MARIA A RUPNICK的其他文献

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{{ truncateString('MARIA A RUPNICK', 18)}}的其他基金

Role of Vessel Maturity in Antiangiogenic Drug Efficacy
血管成熟度在抗血管生成药物疗效中的作用
  • 批准号:
    6777785
  • 财政年份:
    2004
  • 资助金额:
    $ 12.24万
  • 项目类别:
Role of Vessel Maturity in Antiangiogenic Drug Efficacy
血管成熟度在抗血管生成药物疗效中的作用
  • 批准号:
    6892930
  • 财政年份:
    2004
  • 资助金额:
    $ 12.24万
  • 项目类别:
Vessel Maturation as a Regulator of Tissue Remodeling
血管成熟作为组织重塑的调节器
  • 批准号:
    6802764
  • 财政年份:
    2003
  • 资助金额:
    $ 12.24万
  • 项目类别:
Vessel Maturation as a Regulator of Tissue Remodeling
血管成熟作为组织重塑的调节器
  • 批准号:
    7122070
  • 财政年份:
    2003
  • 资助金额:
    $ 12.24万
  • 项目类别:
Vessel Maturation as a Regulator of Tissue Remodeling
血管成熟作为组织重塑的调节器
  • 批准号:
    7272693
  • 财政年份:
    2003
  • 资助金额:
    $ 12.24万
  • 项目类别:
Vessel Maturation as a Regulator of Tissue Remodeling
血管成熟作为组织重塑的调节器
  • 批准号:
    6942346
  • 财政年份:
    2003
  • 资助金额:
    $ 12.24万
  • 项目类别:
Vessel Maturation as a Regulator of Tissue Remodeling
血管成熟作为组织重塑的调节器
  • 批准号:
    6560665
  • 财政年份:
    2003
  • 资助金额:
    $ 12.24万
  • 项目类别:
CONTROLLED RELEASE OF ATRIAL NATRIURETIC FACTOR
心房钠尿因子的受控释放
  • 批准号:
    2027212
  • 财政年份:
    1997
  • 资助金额:
    $ 12.24万
  • 项目类别:
CONTROLLED RELEASE OF ATRIAL NATRIURETIC FACTOR
心房钠尿因子的受控释放
  • 批准号:
    2900983
  • 财政年份:
    1997
  • 资助金额:
    $ 12.24万
  • 项目类别:
CONTROLLED RELEASE OF ATRIAL NATRIURETIC FACTOR
心房钠尿因子的受控释放
  • 批准号:
    6181904
  • 财政年份:
    1997
  • 资助金额:
    $ 12.24万
  • 项目类别:

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