Treatment of lupus nephritis with nanoparticles that selectively target kidney glomeruli
用选择性靶向肾小球的纳米颗粒治疗狼疮性肾炎
基本信息
- 批准号:10679184
- 负责人:
- 金额:$ 57.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AmericanAutoimmune DiseasesBindingBiodistributionBiologicalBloodCellsChitosanCollagen Type IVCoupledCouplingDataDendritic CellsDepositionDevelopmentDiseaseDoseDrug Delivery SystemsDrug KineticsDrug TargetingEncapsulatedEnd stage renal failureEndotheliumEvaluationExhibitsExtravasationFenestrated CapillaryFlow CytometryFluorescent DyesGene DeliveryGlomerular Filtration RateGoalsHistologyHistopathologyHourImmuneImmune ToleranceImmune responseImmunoglobulin GIn VitroIncidenceInjectionsKidneyKidney GlomerulusLabelLaboratoriesLiposomesLiquid substanceLiverLupusLupus NephritisMorbidity - disease rateMorphologyMusNephronsParticle SizePathogenesisPatientsPeptidesPharmaceutical PreparationsProteinuriaRegulatory T-LymphocyteRenal functionRoleSafetySignal TransductionSiteSpleenSymptomsSystemSystemic Lupus ErythematosusTechniquesTherapeuticTherapeutic immunosuppressionValidationbiomaterial compatibilitycontrolled releasecrosslinkdesignglomerular basement membraneimprovedin vivoinnovationlocal drug deliverylupus prone micemortalitymouse modelnanoparticlenanoparticle deliverynew therapeutic targetnovelnovel therapeutic interventionprednisoloneside effectsingle-cell RNA sequencingsurface coatingtargeted treatmenttherapeutic nanoparticlestherapeutic targettooltranscriptome sequencingtripolyphosphatezeta potential
项目摘要
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. Lupus nephritis is the renal
involvement in SLE with predominate glomerulus damage and exhibits a wide variety of symptoms from
asymptomatic proteinuria to end-stage renal disease. Lupus nephritis requires aggressive immunosuppressive
therapy, however, unfortunately most of these medications are associated with severe side effects. Therefore,
development of new treatment strategies is essential.
The goal of this proposal is to develop a nanoparticle delivery system that enables targeted drug delivery with
stable and sustained release of prednisolone at the glomeruli as a novel therapeutic approach for lupus nephritis.
Collagen IV (Col4)-α3,4 and 5 are expressed in the glomerular basement membrane (GBM), which is the only
site in the body that Col4 has direct contact with blood via fenestrated capillary endothelium. Liposomes are one
of the most widely used carriers due to their excellent biocompatibility and non-immunogenicity, but are lack of
stability in terms of leakage of the encapsulated contents. Tripolyphosphate (TPP) cross-linked chitosan
nanoparticles are characterized with controlled release of the loaded contents. Consequently, we hypothesize
that by coupling Col4 binding peptides on the shell of liposomes filled with TPP-chitosan nanoparticles, we would
make a kidney glomerulus selective delivery system with stable and sustained release of the loaded contents.
We further hypothesize that this system loaded with prednisolone exhibits highly therapeutic efficiency due to
the locally sustained drug release at a high concentration, meanwhile, it significantly minimizes the systemic side
effects due to the very low dose of total prednisolone administered.
系统性红斑狼疮(SLE)是一种典型的自身免疫病。狼疮性肾炎是指肾脏
以肾小球损害为主的系统性红斑狼疮,并表现出多种症状
无症状蛋白尿到终末期肾病。狼疮性肾炎需要积极的免疫抑制
然而,不幸的是,大多数这些药物都与严重的副作用有关。因此,
开发新的治疗策略是至关重要的。
这项提议的目标是开发一种纳米颗粒递送系统,该系统能够通过
强的松龙在肾小球的稳定和持续释放是狼疮性肾炎的一种新的治疗方法。
IV型胶原(COL4)-α3、4和5在肾小球基底膜表达,是唯一的
体内COL4通过有孔的毛细血管内皮细胞与血液直接接触的部位。脂质体是一种
由于其良好的生物相容性和非免疫原性,是使用最广泛的载体之一,但缺乏
在密封内容物泄漏方面的稳定性。三聚磷酸盐(TPP)交联壳聚糖
纳米颗粒的特征是对所加载的内容物进行控制释放。因此,我们假设
通过将COL4结合肽偶联到填充了TPP-壳聚糖纳米颗粒的脂质体外壳上,我们将
制备稳定、持续释放所载内容物的肾小球选择性给药系统。
我们进一步假设,该系统负载强的松龙显示出很高的治疗效率,因为
在高浓度的局部药物缓释的同时,它显著减少了全身副作用
由于总剂量很小的强的松龙所致的效果。
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)
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RUISHENG LIU其他文献
RUISHENG LIU的其他文献
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{{ truncateString('RUISHENG LIU', 18)}}的其他基金
Tubuloglomerular feedback response in AKI to CKD transition
AKI 向 CKD 转变中的肾小球反馈反应
- 批准号:
10533630 - 财政年份:2022
- 资助金额:
$ 57.92万 - 项目类别:
Role of tubuloglomerular feedback in the development of hypertension in diabetes
肾小球反馈在糖尿病高血压发生中的作用
- 批准号:
9917816 - 财政年份:2019
- 资助金额:
$ 57.92万 - 项目类别:
Role of tubuloglomerular feedback in the development of hypertension in diabetes
肾小球反馈在糖尿病高血压发生中的作用
- 批准号:
10394215 - 财政年份:2019
- 资助金额:
$ 57.92万 - 项目类别:
Renal hemodynamics and hypertension during pregnancy
妊娠期肾脏血流动力学和高血压
- 批准号:
10090619 - 财政年份:2018
- 资助金额:
$ 57.92万 - 项目类别:
Primary cilia and modulation of the renal microcirculation
原发纤毛和肾微循环的调节
- 批准号:
8895614 - 财政年份:2014
- 资助金额:
$ 57.92万 - 项目类别:
Primary cilia and modulation of the renal microcirculation
原发纤毛和肾微循环的调节
- 批准号:
8692309 - 财政年份:2014
- 资助金额:
$ 57.92万 - 项目类别:
Primary cilia and modulation of the renal microcirculation
原发纤毛和肾微循环的调节
- 批准号:
8817288 - 财政年份:2014
- 资助金额:
$ 57.92万 - 项目类别:
Primary cilia and modulation of the renal microcirculation
原发纤毛和肾微循环的调节
- 批准号:
9282582 - 财政年份:2014
- 资助金额:
$ 57.92万 - 项目类别:
Primary cilia and modulation of the renal microcirculation
原发纤毛和肾微循环的调节
- 批准号:
9068089 - 财政年份:2014
- 资助金额:
$ 57.92万 - 项目类别:
Tubuloglomerular feedback and salt-sensitive hypertension
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- 批准号:
9068087 - 财政年份:2013
- 资助金额:
$ 57.92万 - 项目类别:
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