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
- 来源:
- 关键词:
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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{{ 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:
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