Research Supplement to Promote Diversity: Carlos Torres (R03EB031495 Parent Award)

促进多样性的研究补充：Carlos Torres（R03EB031495 家长奖）

基本信息

批准号：
10592146
负责人：
Kevin James McHugh
金额：
$ 1.5万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2022-12-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Every year an estimated 19.4 million children do not receive the set of vaccines recommended by the World Health Organization, leading to 1.5 million vaccine-preventable deaths.1,2 A majority of undervaccinated children live in low- and middle-income countries and often have limited access to healthcare.2,3 Nearly 6 million of these children receive at least one vaccine dose, but remain at risk because they have not completed the full dosing regimen.4,5 A vaccination method that delivers all doses of a vaccine, or multiple vaccines, in a single injection would enable children with even one-time access to healthcare to be fully protected from the corresponding infectious disease. Unfortunately, most controlled-release drug delivery systems exhibit continuous release kinetics, which is vastly different from traditional soluble vaccines administered in multiple discrete doses over a course of months. One recent study has described the development of biodegradable microparticle platform with a polymer shell encapsulating a vaccine-loaded core that exhibits delayed, pulsatile release after a period determined by the polymer degradation rate.6 By injecting patients with a mixed population of particles with different degradation rates, vaccine can be released as discrete pulses, thereby mimicking traditional vaccination schedules known to be safe and effective. Unfortunately, the original microparticle production method negatively affects antigen stability, requires the use of large-gauge needles, and is low-throughput. This project seeks to overcome these challenges by preparing microparticles using coaxial electrospraying, a single-step fabrication process that can produce a single aqueous, vaccine-loaded core surrounded by a shell of polymer. The parent proposal first aims to create small core-shell microparticles with dense polymeric shells that demonstrate the delayed, pulsatile release of macromolecules in vitro and in vivo using fluorescently-labeled model molecules and reporter proteins to assess protein stability within the microparticles. This diversity supplement will expand the scope of work previously proposed to support the work of Carlos Torres, a Hispanic male undergraduate student at Houston Community College, including the investigation of coaxial electrospraying parameters between pieces of electrospraying equipment. The goal of Carlos’s work is to identify the key features that affect core-shell microparticle morphology and release kinetics and develop solutions that allows electrospraying conditions to be readily transferred between different pieces of equipment. If successful, Carlos’s work will enhance the reproducibility of science and allow different research groups to work in unison to improve electrosprayed particle formulations for single-injection vaccination as well as other drug delivery applications. Ultimately, these particles could serve as a key tool in the fight against infectious disease both in the developing world where resources are limited and in the developed world, where uninsured children and rural communities show consistently lower vaccination coverage.7

项目概要/摘要每年估计有 1940 万儿童没有接种世界推荐的疫苗卫生组织，导致 150 万人因疫苗可预防的死亡。1,2 大多数儿童未接种疫苗生活在低收入和中等收入国家，获得医疗保健的机会往往有限。2,3 其中近 600 万人儿童至少接受了一剂疫苗，但由于尚未完成全部剂量，因此仍面临风险方案 4,5 在单次注射中提供所有剂量的疫苗或多种疫苗的疫苗接种方法将使即使是一次性获得医疗保健的儿童也能得到充分保护，免受相应的影响不幸的是，大多数控释药物递送系统表现出连续释放。动力学，这与传统的可溶性疫苗在一段时间内以多个离散剂量施用有很大不同最近的一项研究描述了可生物降解微粒平台的开发。聚合物外壳封装了负载疫苗的核心，在一段时间后表现出延迟的脉冲释放由聚合物降解率决定。6 通过向患者注射混合颗粒群不同的降解率，疫苗可以作为离散脉冲释放，从而模仿传统的疫苗接种不幸的是，原来的微粒生产方法被认为是安全有效的。影响抗原稳定性，需要使用大规格针头，并且通量低。通过使用同轴电喷雾（一步制造）制备微粒来克服这些挑战该过程可以产生由聚合物外壳包围的单一水性、负载疫苗的核心。该提案的第一个目标是创建具有致密聚合物壳的小核壳微粒，以证明使用荧光标记的模型分子在体外和体内延迟、脉动释放大分子和报告蛋白以评估微粒内的蛋白质稳定性。这种多样性补充将得到扩展。先前提议支持西班牙裔男本科生卡洛斯·托雷斯 (Carlos Torres) 工作的工作范围休斯顿社区学院的学生，包括同轴电喷雾参数的研究卡洛斯的工作目标是确定影响电喷涂设备之间的关键特征。核壳微粒形态和释放动力学，并开发允许电喷雾的解决方案如果成功的话，卡洛斯的工作将能够在不同设备之间轻松转移。提高科学的可重复性，并允许不同的研究小组协同工作以改进用于单次注射疫苗接种以及其他药物输送应用的电喷雾颗粒制剂。最终，这些颗粒可以成为发展中国家对抗传染病的关键工具。资源有限的世界以及儿童和农村社区没有保险的发达国家疫苗接种覆盖率持续较低。7