Thermally Responsive Magnetic-Hydrogel Nanocomposites for Advanced Drug Delivery

用于先进药物输送的热响应磁水凝胶纳米复合材料

• 批准号: 8339884
• 负责人: NICHOLAS A PEPPAS
• 金额: $ 18.08万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8339884
• 关键词: Address; Adsorption; Adverse effects; Affect; Antibodies; Behavior; Binding; Biomedical Engineering; Blood; Blood Circulation; Cell Surface Receptors; Cells; Characteristics; Charge; Deposition; Development; Diffusion; Dose; Drug Carriers; Drug Delivery Systems; Drug Transport; Encapsulated; Equilibrium; Ethylene Glycols; Fever; Frequencies; Gel; Gold; Half-Life; Heating; Hydrogels; Image; Immune; Immunoglobulin G; Implant; Kinetics; Light; Location; Magnetic Resonance Imaging; Magnetism; Medical Imaging; Metals; Modeling; Morphology; N-isopropylacrylamide; NanoGel; Nanosphere; Particulate; Penetration; Performance; Pharmaceutical Preparations; Pharmacotherapy; Photons; Physiological; Polymers; Positioning Attribute; Property; Proteins; Research; Research Personnel; Research Project Grants; Shapes; Solvents; Surface; Swelling; System; Systems Development; Temperature; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Work; absorption; base; biomaterial compatibility; chemical stability; clinically relevant; crosslink; density; design; environmental change; ethylene glycol; hydrophilicity; improved; in vitro testing; in vivo; iron oxide; magnetic field; metal oxide; nanocarrier; nanocomposite; nanomaterials; nanoparticle; nanoshell; novel; overexpression; particle; physical property; receptor; research study; response; solute; spatiotemporal; success; uptake

DESCRIPTION (provided by applicant): This is a revised proposal for an R21 Exploratory / Developmental Bioengineering Research Grant (EBRG) under PA-10-010 as an investigator-initiated application for developing a nanocomposite drug delivery system. The proposed drug delivery system consists of a degradable, thermally-responsive hydrogel nanosphere encapsulating a single domain paramagnetic iron oxide nanoparticle to release drug by swelling once magnetically-triggered. AC inductive heating of the magnetic nanoparticle conducts heat into the surrounding 'nanogel', which forces it to swell and imbibe physiological solvent. The swollen gel then releases incorporated drug agents for localized therapeutic delivery by diffusion and convective currents created during cyclical swelling and collapsing. The carriers will be designed for optimal in vivo targeting utility based on size, shape, charge, deformability, hydrophilicity, and degradability. Additionally, nanogel carriers will be surface modified for immune 'stealthing' to prolong circulation times, and with antibodies to facilitate active targeting. This composite drug delivery system can be used to concentrate therapeutics locally with release initiated by an external triggering mechanism and with enhanced medical imaging contrast if desired. In the development of this system, several fundamental challenges regarding nanogel drug delivery will be addressed. Specifically, the impact of temperature excursions and volume swelling responses will be examined to determine their impact on carrier stability, active targeting, and on non-specific protein adsorption. Furthermore, a novel testing apparatus will be fabricated that allows for swelling kinetics experiments as a function of carrier size. This will allow predictions to be made as to time to equilibrium and solute transport times with very small particulate carriers. Specific antibodies have been selected to enhance uptake by targeted cells overexpressing the desired receptor. Finally, nanocarriers will be tested in vitro to establish cytocompatibility, uptake performance, and required magnetic field strengths for triggering.

描述（由申请人提供）：这是对PA-10-010下的R21探索性 /发育生物工程研究赠款（EBRG）的修订建议，作为研究者发起的纳米复合药物输送系统的研究申请。所提出的药物输送系统由可降解的，热响应的水凝胶纳米层封装，封装了单个结构域的氧化铁氧化铁纳米颗粒，一旦磁触发，可以通过肿胀来释放药物。磁性纳米颗粒的交流电感加热向周围的“纳米凝胶”进行热量，从而迫使其膨胀和吸收生理溶剂。然后，肿胀的凝胶将掺入的药物释放，以通过在周期性肿胀和崩溃期间产生的扩散和对流电流进行局部治疗递送。该载体将根据大小，形状，充电性，可变形性，亲水性和降解性而设计为最佳体内靶向实用性。此外，将对纳米凝胶载体进行表面修饰，以通过延长循环时间，并具有抗体以促进主动靶向。该复合药物输送系统可用于将治疗剂浓缩，并通过外部触发机制引发的释放，并具有增强的医学成像对比度。 在该系统的开发中，将解决有关纳米凝胶药物输送的一些基本挑战。具体而言，将检查温度偏移和体积肿胀反应的影响，以确定它们对载体稳定性，主动靶向和非特异性蛋白质吸附的影响。此外，将制造出一种新型的测试设备，允许溶胀动力学实验随载体大小的函数。这将允许对具有非常小的颗粒载体的平衡和溶质传输时间进行预测。已经选择了特定的抗体来通过过表达所需受体的靶向细胞来增强摄取。最后，将在体外测试纳米载体，以建立细胞相容性，吸收性能以及所需的磁场强度以触发。