Efficacy of the Microsphere-Thermo-Responsive Hydrogel Ocular Drug Delivery System
微球热响应水凝胶眼部给药系统的功效
基本信息
- 批准号:9099053
- 负责人:
- 金额:$ 41.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2020-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdverse effectsAffectAge related macular degenerationAnimal ModelAvastinBiocompatible MaterialsBiodegradable microsphereBlood VesselsBolus InfusionCataractChoroidal NeovascularizationClinicalClinical ResearchClinical TrialsComparative StudyDataDevicesDiabetic RetinopathyDiseaseDoseDrug Delivery SystemsElectroretinographyEmulsionsEncapsulatedEndophthalmitisEndothelial CellsFamily memberFrequenciesGlycolatesGoalsHealthcare SystemsHemorrhageHistologyHydrogelsImageIn VitroInjectableInjection of therapeutic agentKnowledgeLasersLucentisMeasuresMethodsMicrospheresMindMitogensMonitorNeedlesOne-Step dentin bonding systemOphthalmoscopesOptical Coherence TomographyPatientsPharmaceutical PreparationsPosterior eyeball segment structureProteinsRegimenRetinalRetinal DetachmentRetinal PerforationsRodent ModelScanningSiteSystemTechniquesTechnologyTestingTherapeutic EffectTimeTranslationsTreatment EfficacyVascular DiseasesVascular Endothelial Growth FactorsVascular PermeabilitiesVisual AcuityWorkangiogenesisbasebevacizumabbiomaterial compatibilityblood flow measurementclinical practicecomparative efficacycontrolled releaseconventional therapyefficacy testingimaging modalityin vitro Modelin vivoin vivo Modelpublic health relevanceranibizumabresponsetreatment trial
项目摘要
DESCRIPTION (provided by applicant): Recently employed intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is a very promising treatment for the wet form of age-related macular degeneration and diabetic retinopathy. While the therapeutic effects are positive, a major drawback is that this treatment must be repeated every four to six weeks. This is not a desirable treatment method as it is associated with several inherent complications. No currently available device can deliver anti-VEGF in a sustained manner. Hence, there is a great need for a relatively non-invasive delivery system that is more effective than the current clinical
regimen. Recently, we have developed a biodegradable microspheres, thermo-responsive hydrogel ocular drug delivery system. Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres are produced using our modified double emulsion technique providing a better microenvironment for protein-based pharmacological agents. The thermo-responsive hydrogel is a safe, effective, and injectable biomaterial that is used to encapsulate and release various agents. The hydrogel will be used to confine the microspheres to a specific delivery site. We have established both a controlled sustained release of anti-VEGF for a period of 6 months and excellent biocompatibility of the proposed drug delivery system. The overall goal of this proposal is to demonstrate the efficacy of our proposed drug delivery in both in vitro and in vivo systems and by comparing to the conventional therapy. The hypothesis is that a sustained controlled anti-VEGF release over a prolong period of ~6 months will be as effective, if not more effective, as the conventional therapy. The goal of Specific Aim 1 is to quantitatively compare the efficacy and bioactivity of the proposed drug delivery system to the conventional therapy in its ability to suppress angiogenic responses in both in vitro and in vivo models. Specific Aim 1 will be accomplished in two parts: 1a testing bioactivity of released anti-VEGF agent in an in vitro model and 1b comparing the bioactivity and treatment efficacy via time-released anti-VEGF agents to conventional treatment in a laser-induced choroidal neovascularization (CNV) rodent model. The goal of Specific Aim 2 is to measure long-term efficacy and monitor for potential side effects, if any, of the proposed drug delivery system in an in vivo model. Long-term efficacy and potential side effects will be monitored through electroretinogram (ERG) responses, scanning laser ophthalmoscope (SLO)-vascular imaging blood flow measurements, spectral- domain optical coherence tomography (SD-OCT) and histological examination (at endpoint) in both control and treated groups. Widespread clinical use of anti-VEGF necessitates a practical and effective delivery method to the posterior segment of the eye. The knowledge gained in this proposal will bring this technology one step closer to translation into the clinical practice. We believe that our drug delivery system will provide a practical and effective method to deliver anti
VEGF agents. The system will have a significant impact on the current healthcare system by reducing the frequency of injections and providing benefits of sustained treatment.
描述(由申请人提供):最近采用的玻璃体内抗血管内皮生长因子(抗VEGF)疗法是治疗湿性年龄相关性黄斑变性和糖尿病视网膜病变的非常有前途的疗法。虽然治疗效果是积极的,但一个主要缺点是这种治疗必须每四至六周重复一次。这不是一种理想的治疗方法,因为它与几种固有的并发症有关。目前没有可用的装置可以以持续的方式递送抗VEGF。因此,非常需要一种相对非侵入性的递送系统,其比目前的临床递送系统更有效。
方案.最近,我们开发了一种可生物降解的微球、热响应性水凝胶眼部给药系统。生物可降解的聚(乳酸-羟基乙酸)(PLGA)微球的生产使用我们改进的复乳技术,提供了一个更好的微环境,蛋白质为基础的药物。热响应性水凝胶是一种安全、有效、可注射的生物材料,用于封装和释放各种药物。水凝胶将用于将微球限制在特定的递送部位。我们已经建立了一个为期6个月的抗VEGF的控制缓释和良好的生物相容性的拟议药物输送系统。本提案的总体目标是通过与传统疗法进行比较,证明我们提出的药物递送在体外和体内系统中的功效。假设在约6个月的延长时间内持续控制的抗VEGF释放将与常规疗法一样有效,如果不是更有效的话。具体目标1的目的是定量比较拟定药物递送系统与常规治疗在体外和体内模型中抑制血管生成反应的能力方面的疗效和生物活性。具体目标1将分两部分完成:1a在体外模型中测试释放的抗VEGF剂的生物活性,1b在激光诱导的脉络膜新生血管形成(CNV)啮齿动物模型中比较通过时间释放的抗VEGF剂与常规治疗的生物活性和治疗功效。具体目标2的目标是在体内模型中测量拟定给药系统的长期疗效并监测潜在副作用(如有)。在对照组和治疗组中,将通过视网膜电图(ERG)反应、扫描激光检眼镜(SLO)-血管成像血流测量、光谱域光学相干断层扫描(SD-OCT)和组织学检查(终点)监测长期疗效和潜在副作用。抗VEGF的广泛临床应用需要一种实用且有效的眼后段递送方法。本提案中获得的知识将使该技术更接近于转化为临床实践。我们相信,我们的药物传递系统将提供一个实用和有效的方法,
VEGF试剂。该系统将通过减少注射频率和提供持续治疗的益处,对当前的医疗保健系统产生重大影响。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Bioactive Aflibercept In Vitro.
- DOI:10.1080/02713683.2018.1533983
- 发表时间:2019-03
- 期刊:
- 影响因子:2
- 作者:Liu W;Lee BS;Mieler WF;Kang-Mieler JJ
- 通讯作者:Kang-Mieler JJ
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JENNIFER J Kang-Mieler其他文献
JENNIFER J Kang-Mieler的其他文献
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{{ truncateString('JENNIFER J Kang-Mieler', 18)}}的其他基金
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$ 41.99万 - 项目类别:
Dynamic Tracer Kinetic Model to Detect Preclinical Diabetic Retinopathy (DR)
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- 批准号:
10612529 - 财政年份:2021
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$ 41.99万 - 项目类别:
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Sustained Ocular Drug Delivery System for Anti-VEGF Agents
抗 VEGF 药物持续眼部给药系统
- 批准号:
10363699 - 财政年份:2019
- 资助金额:
$ 41.99万 - 项目类别:
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10608062 - 财政年份:2019
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9918421 - 财政年份:2019
- 资助金额:
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10645936 - 财政年份:2019
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