Episodic Release of GnRH from Pulsating Hydrogels

脉动水凝胶中 GnRH 的间歇性释放

基本信息

  • 批准号:
    6717721
  • 负责人:
  • 金额:
    $ 25.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-04-01 至 2007-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to develop an implantable polymeric device, which delivers gonadotropin releasing hormone(GnRH, aka leuteinizing hormone release hormone, or LHRH) in periodic pulses, mimicking the normal, ultradian endogenous rhythm. Rhythmic pulsed administration of GnRH has been used successfully in the induction of ovulation in amenorrhic women, and in the induction of puberty and maintenance of sexual maturity in both males and females with hypogonadotropic hypogonadism (HH), while continuous administration of GnRH fails. Present pulsatile treatment is administered using wearable pumps, with cutaneous breach by a catheter. For patients who must receive pulsatile GnRH for many years, this mode of delivery leads to significant inconvenience and danger of infection. The proposed device could be implanted subcutaneously or intraperitoneally, and may function for months or years. It is hoped that implantation will ameliorate the disadvantages of pump/catheter systems. The device concept features a hydrogel membrane, which undergoes periodic swelling-deswelling cycles, due to a feedback interaction between the membrane with the enzyme glucose oxidase. Release occurs during the swollen phase of the cycle. Oscillations are "fueled" by endogenous glucose at the site of implantation, whose level fluctuates only moderately in nondiabetics. (Rhythmic behavior of this device is distinguished from the glucose-responsive behavior of closed-loop insulin delivery devices.) While the feasibility of this concept has been confirmed in a model system, considerable work remains in converting the concept to a workable device that can be tested in patients. The specific goal of this proposal is to produce a prototype system whose properties can be tested in an in vitro environment that emulates in vivo conditions. In pursuing this goal, effects of the hydrogel membrane composition and thickness, the enzyme reaction, the device geometry, and the molecular properties of GnRH on the pulsatile release pattern will be studied. We will investigate device behavior in buffers and simulated plasma, when challenged with constant levels of glucose and programs of glucose fluctuations that are observed in nondiabetic individuals.
描述(由申请人提供): 该研究的长期目标是开发一种可植入聚合物装置,以周期性脉冲输送促性腺激素释放激素(GnRH,又名黄体生成素释放激素,或 LHRH),模仿正常的超电内源性节律。 GnRH 的节律脉冲给药已成功用于诱导闭经女性排卵,以及诱导性腺激素减退症 (HH) 男性和女性青春期的诱导和性成熟的维持,而连续给药 GnRH 则失败。目前的脉冲治疗是使用可穿戴泵进行的,通过导管造成皮肤破裂。对于必须多年接受脉冲式 GnRH 的患者来说,这种输送方式会带来极大的不便和感染的危险。所提出的装置可以植入皮下或腹膜内,并且可以运行数月或数年。希望植入能够改善泵/导管系统的缺点。该装置概念的特点是水凝胶膜,由于膜与葡萄糖氧化酶之间的反馈相互作用,该膜经历周期性的膨胀-消膨胀循环。释放发生在周期的肿胀阶段。振荡是由植入部位的内源性葡萄糖“推动”的,其水平在非糖尿病患者中仅适度波动。 (该装置的节律行为与闭环胰岛素输送装置的葡萄糖响应行为不同。)虽然这一概念的可行性已在模型系统中得到证实,但将这一概念转化为可在患者身上进行测试的可行装置仍有大量工作要做。该提案的具体目标是生产一个原型系统,其特性可以在模拟体内条件的体外环境中进行测试。为了实现这一目标,将研究水凝胶膜组成和厚度、酶反应、装置几何形状以及 GnRH 分子特性对脉冲释放模式的影响。当受到恒定水平的葡萄糖和在非糖尿病个体中观察到的葡萄糖波动程序的挑战时,我们将研究缓冲液和模拟血浆中的设备行为。

项目成果

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

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Ronald A Siegel其他文献

Chirally Pure Prodrugs and Their Converting Enzymes Lead to High Supersaturation and Rapid Transcellular Permeation of Benzodiazepines.
手性纯前药及其转化酶导致苯二氮卓类药物的高过饱和度和快速跨细胞渗透。
  • DOI:
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mamta Kapoor;Narsihmulu Cheryala;Davin Rautiola;Gunda I Georg;James C. Cloyd;Ronald A Siegel
  • 通讯作者:
    Ronald A Siegel
Miscibility of Amorphous Solid Dispersions: A Rheological and Solid-state NMR Spectroscopy Study.
无定形固体分散体的混溶性:流变学和固态核磁共振波谱研究。
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Sichen Song;Jianchao Xu;Zhenxuan Chen;Changquan Calvin Sun;Eric J Munson;Ronald A Siegel
  • 通讯作者:
    Ronald A Siegel

Ronald A Siegel的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Ronald A Siegel', 18)}}的其他基金

Implantable Glucose Microsensor for Wireless Telemetry
用于无线遥测的植入式血糖微传感器
  • 批准号:
    7686517
  • 财政年份:
    2008
  • 资助金额:
    $ 25.68万
  • 项目类别:
Novel MEMS and Microfluidic Platforms for Drug Delivery
用于药物输送的新型 MEMS 和微流体平台
  • 批准号:
    6738869
  • 财政年份:
    2003
  • 资助金额:
    $ 25.68万
  • 项目类别:
Episodic Release of GnRH from Pulsating Hydrogels
脉动水凝胶中 GnRH 的间歇性释放
  • 批准号:
    6618562
  • 财政年份:
    2003
  • 资助金额:
    $ 25.68万
  • 项目类别:
Episodic Release of GnRH from Pulsating Hydrogels
脉动水凝胶中 GnRH 的间歇性释放
  • 批准号:
    7026544
  • 财政年份:
    2003
  • 资助金额:
    $ 25.68万
  • 项目类别:
Novel MEMS and Microfluidic Platforms for Drug Delivery
用于药物输送的新型 MEMS 和微流体平台
  • 批准号:
    6795967
  • 财政年份:
    2003
  • 资助金额:
    $ 25.68万
  • 项目类别:
Episodic Release of GnRH from Pulsating Hydrogels
脉动水凝胶中 GnRH 的间歇性释放
  • 批准号:
    6876591
  • 财政年份:
    2003
  • 资助金额:
    $ 25.68万
  • 项目类别:
SMALL INSTRUMENTATION PROGRAM
小型仪器项目
  • 批准号:
    3524053
  • 财政年份:
    1988
  • 资助金额:
    $ 25.68万
  • 项目类别:
IMPLANTABLE SELF-REGULATING OSMOTIC INSULIN PUMP
植入式自调节渗透胰岛素泵
  • 批准号:
    3237160
  • 财政年份:
    1987
  • 资助金额:
    $ 25.68万
  • 项目类别:
IMPLANTABLE SELF-REGULATING OSMOTIC INSULIN PUMP
植入式自调节渗透胰岛素泵
  • 批准号:
    3237155
  • 财政年份:
    1987
  • 资助金额:
    $ 25.68万
  • 项目类别:
IMPLANTABLE SELF-REGULATING OSMOTIC INSULIN PUMP
植入式自调节渗透胰岛素泵
  • 批准号:
    3237161
  • 财政年份:
    1987
  • 资助金额:
    $ 25.68万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了