Localized delivery of glycosaminoclycan ethers for the treatment of radiation-induced proctitis

局部递送糖胺聚糖醚治疗放射性直肠炎

基本信息

  • 批准号:
    10530585
  • 负责人:
  • 金额:
    $ 30.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-12-01 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

ABSTRACT Radiation-induced proctitis (RIP) is often considered a chronic inflammatory disease involving the rectum. Pathologic studies have shown patient symptoms are correlated with inflammatory lesions along the epithelium lining the rectum. This grant application proposes to combine novel sulfated anionic polysaccharides, semisynthetic glycosaminoglycan ethers (SAGEs) with silk- elastinlike protein polymer (SELP) matrices to deliver therapeutically relevant doses in the rectum via a precisely engineered in situ gelling enema. SELPs exist as aqueous solutions at room temperature, and form a solid hydrogel matrix at body temperature, enabling them to prevent rapid clearance of the SAGE and enhance its localization in the lumen of the rectum and lower bowel. We hypothesize that localized delivery of SAGE can protect the rectum from damage caused by radiotherapy and improve efficacy by ameliorating RIP. To test this hypothesis three specific aims are proposed: 1) To synthesize and characterize SELPs with appropriate rheological properties and release profiles for rectal delivery of SAGE; 2) To investigate the biodistribution and efficacy of SAGE delivered from SELP hydrogels in a murine model of radiation-induced proctitis; 3) To elucidate mast cells as a key effector cell type in radiation-induced proctitis and assess SAGE in SELP hydrogels’ ability to attenuate mast cell mediated proctitis. This proposal is translational in nature and innovative in the new indication for use of recombinant SELPs to deliver our patented SAGE compounds with potent anti-inflammatory and anti-pain properties. The project is significant in that it will reduce the adverse effects of RIP in the affected patient populations. This work will establish the early-stage preclinical validation for these two systems and provide detailed knowledge about the inflammation and pain attenuation properties of the SAGE-SELP compounds.
摘要 放射性直肠炎(RIP)通常被认为是一种慢性炎症性疾病,涉及 直肠。病理学研究表明,患者的症状与炎症有关。 沿着直肠衬里上皮的病变。这项拨款申请建议将小说 硫酸化阴离子多糖,半合成糖胺聚糖醚(SAGES)与丝绸- 在直肠内提供治疗相关剂量的弹性蛋白聚合物(SELP)基质 通过一种精心设计的原位凝胶灌肠。SELP在房间中以水溶液的形式存在 温度,并在体温下形成固体水凝胶基质,使它们能够防止 快速清除鼠尾草并增强其在直肠和直肠下腔的定位 肠子。我们假设局部注射鼠尾草可以保护直肠免受损伤。 通过改善RIP来提高疗效。为了检验这一假说,有三个 具体目标是:1)合成和表征具有合适流变性的SELP 鼠尾草经直肠给药的性质及释药特性;2)考察其生物分布 SELP水凝胶提供的鼠尾草对辐射诱导小鼠模型的疗效 3)阐明肥大细胞在放射性直肠炎中的关键效应细胞类型,以及 评估SELP水凝胶中的SAGE减轻肥大细胞介导的直肠炎的能力。这项建议 是翻译性质的,并在使用重组SELP的新适应症方面具有创新性 提供我们的专利鼠尾草化合物,具有强大的抗炎和止痛特性。 该项目意义重大,因为它将减少RIP对受影响患者的不良影响 人口。这项工作将为这两个系统建立早期的临床前验证 并提供有关消炎止痛属性的详细知识 鼠尾草-SELP化合物。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Vascular permeability in chronic rhinosinusitis enhances accumulation and retention of nanoscale pegylated liposomes.
慢性鼻窦炎的血管通透性增强了纳米级聚乙二醇化脂质体的积累和保留。
  • DOI:
    10.1016/j.nano.2021.102453
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Khurana,Nitish;Yathavan,Bhuvanesh;Jedrzkiewicz,Jolanta;Gill,AmarbirS;Pulsipher,Abigail;Alt,JeremiahA;Ghandehari,Hamidreza
  • 通讯作者:
    Ghandehari,Hamidreza
An Oligomeric Sulfated Hyaluronan and Silk-Elastinlike Polymer Combination Protects against Murine Radiation Induced Proctitis.
  • DOI:
    10.3390/pharmaceutics14010175
  • 发表时间:
    2022-01-12
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Steinhauff D;Jensen MM;Griswold E;Jedrzkiewicz J;Cappello J;Oottamasathien S;Ghandehari H
  • 通讯作者:
    Ghandehari H
Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis.
  • DOI:
    10.1016/j.jconrel.2021.03.001
  • 发表时间:
    2021-04-10
  • 期刊:
  • 影响因子:
    10.8
  • 作者:
    Steinhauff, D.;Jensen, M.;Talbot, M.;Jia, W.;Isaacson, K.;Jedrzkiewicz, J.;Cappello, J.;Oottamasathien, S.;Ghandehari, H.
  • 通讯作者:
    Ghandehari, H.
Liquid-cell transmission electron microscopy for imaging of thermosensitive recombinant polymers.
  • DOI:
    10.1016/j.jconrel.2022.02.019
  • 发表时间:
    2022-04
  • 期刊:
  • 影响因子:
    10.8
  • 作者:
    Isaacson, Kyle J.;Van Devener, Brian R.;Steinhauff, Douglas B.;Jensen, M. Martin;Cappello, Joseph;Ghandehari, Hamidreza
  • 通讯作者:
    Ghandehari, Hamidreza
Matrix Mediated Viral Gene Delivery: A Review.
  • DOI:
    10.1021/acs.bioconjchem.8b00853
  • 发表时间:
    2019-02
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    D. Steinhauff;H. Ghandehari
  • 通讯作者:
    D. Steinhauff;H. Ghandehari
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Hamid Ghandehari其他文献

Hamid Ghandehari的其他文献

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{{ truncateString('Hamid Ghandehari', 18)}}的其他基金

Localized delivery of glycosaminoclycan ethers for the treatment of radiation-induced proctitis
局部递送糖胺聚糖醚治疗放射性直肠炎
  • 批准号:
    10296670
  • 财政年份:
    2018
  • 资助金额:
    $ 30.41万
  • 项目类别:
Localized delivery of glycosaminoclycan ethers for the treatment of radiation-induced proctitis
局部递送糖胺聚糖醚治疗放射性直肠炎
  • 批准号:
    10058818
  • 财政年份:
    2018
  • 资助金额:
    $ 30.41万
  • 项目类别:
In-situ Gelling Protein Polymer Intravascular Embolic Agent for Hepatic Carcinoma
原位胶凝蛋白聚合物血管内栓塞剂治疗肝癌
  • 批准号:
    8314876
  • 财政年份:
    2012
  • 资助金额:
    $ 30.41万
  • 项目类别:
Targeted Polymeric Combination Delivery for Treatment of Ovarian Cancer
用于治疗卵巢癌的靶向聚合物组合递送
  • 批准号:
    7999063
  • 财政年份:
    2010
  • 资助金额:
    $ 30.41万
  • 项目类别:
Biological fate and biocompatibility of dendritic and silica-based nanoconstructs
树枝状和二氧化硅基纳米结构的生物命运和生物相容性
  • 批准号:
    7615449
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:
Biological fate and biocompatibility of dendritic and silica-based nanoconstructs
树枝状和二氧化硅基纳米结构的生物命运和生物相容性
  • 批准号:
    7916398
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:
Dendritic Biomaterials for Oral Delivery of Chemotherapeutics
用于口服化疗药物的树突状生物材料
  • 批准号:
    7627049
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:
Dendritic Biomaterials for Oral Delivery of Chemotherapeutics
用于口服化疗药物的树突状生物材料
  • 批准号:
    7633399
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:
Biological fate and biocompatibility of dendritic and silica-based nanoconstructs
树枝状和二氧化硅基纳米结构的生物命运和生物相容性
  • 批准号:
    7341354
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:
Dendritic Biomaterials for Oral Delivery of Chemotherapeutics
用于口服化疗药物的树突状生物材料
  • 批准号:
    7848308
  • 财政年份:
    2007
  • 资助金额:
    $ 30.41万
  • 项目类别:

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Disrupted sleep architecture in adolescents with functional abdominal pain disorders
患有功能性腹痛疾病的青少年的睡眠结构被破坏
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    2022
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针对有功能性腹痛风险的幼儿进行基于互联网的预防干预的随机对照试验
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慢性腹痛背后的新型微生物驱动组胺途径
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  • 财政年份:
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  • 资助金额:
    $ 30.41万
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  • 财政年份:
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    $ 30.41万
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Home-based transcutaneous electrical acustimulation for abdominal pain
家庭经皮电针治疗腹痛
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