Engineered Anisotropic Biphasic Nanoparticles for Bio-Therapeutic and Pharmaceutical Technologies

这项研究提出了一种用于各向异性微米和纳米颗粒的新的纳米制造范式，称为Janus粒子。虽然这类颗粒最近受到了很大的关注，但它们的配方与生物技术不兼容，生物技术需要生物良性聚合物，分阶段输送多种生物治疗因子是经常需要的，但很难实现。这项工作的关键目标是创造新型的可生物降解和生物相容的各向异性两相纳米粒子(ABNPs)，用于大规模生产，能够双隔室并结合两种或更多具有交错释放曲线的治疗药物。将追求三个具体目标。目标1重点是设计和合成ABNP/ABMPs平台，该平台具有不同的聚合物和脂质材料的组合，这些材料自组装成各向异性粒子。Aim 2专注于聚合物/聚合物和聚合物/脂质的建模，用于工程ABNP/ABMP的合理设计；Aim 3建议通过将ABNP/ABMP纳米制造范例应用于难以治疗的癌症，展示ABNP/ABMP纳米制造范例对双联药物分阶段递送的更广泛的功能影响。如果该项目成功，将在制药学、生物医学、材料工程和分散稳定方面取得重大进展。此外，多隔室、生物相容的颗粒将构成设计主动和被动药物输送载体、组织工程支架和仿生颗粒的新途径。更广泛的影响是在扩大URM学者参与的机制方面；以及在纳米颗粒制造和药物输送科学和工程工具方面制定课程和专业培训机制。建议了扩大参与的四个具体机制：1)国际和平研究所将为所有参与的学生创建学习单元，以便在联合小组会议上完成和讨论研究结果；2)将结果纳入教学课程和实验室单元；3)积极参与罗格斯大学已经建立的外联计划；4)向国际URM学生进行外联，并在讲习班和会议上传播。

This study proposes a novel nanomanufacturing paradigm for anisotropic micro- and nanoparticles, termed Janus particles. While this class of particles has received much attention recently, their formulations have not been compatible with biotechnology, where bio-benign polymers are called for, and staged delivery of multiple biotherapeutic factors is frequently desired but difficult to achieve. The key goal of this work is to create novel biodegradable and biocompatible anisotropic biphasic nano- particles (ABNPs) for large scale production, capable of dual compartmentalization and incorporation of two or more therapeutic drugs with staggered release profiles. Three specific aims will be pursued. Aim 1 is focused on the design and synthesis of a platform of ABNP/ABMPs with different combinations of polymeric and lipid materials that self-assemble into anisotropic particles. Aim 2 is focused on the modeling of polymer/polymer and polymer/lipid for the rational design of engineered ABNP/ABMP; Aim 3 proposes to demonstrate the broader functional impact of the nanomanufacturing paradigm of ABNP/ABMP on phased delivery of dual-combination drugs by applying these particles for difficult-to-treat cancers.If successful this project will lead to significant advances in pharmaceutics, biomedicine, materials engineering and dispersion stabilization. Furthermore, multicompartmental, biocompatible particles will constitute a new avenue in the design of active and passive drug delivery vehicles, tissue engineering scaffolds, and biomimetic particles. The broader impacts are in the mechanisms for broadening participation of URM scholars; and developing curriculum and professional training mechanisms in the tools for nanoparticle manufacturing and drug delivery science and engineering. Four specific mechanisms for broadening participation are proposed: 1) Study modules will be created by the PI for all participating students to complete and discuss research findings in joint group meetings; 2) Results will be incorporated into teaching courses and laboratory modules; 3) Active participation in already established outreach programs at Rutgers; 4) Outreach to URM students and dissemination in workshops and conferences.