Mechanistic Analysis of Polyelectrolyte-Based Colloidal Drug Carriers

聚电解质胶体药物载体的机理分析

基本信息

  • 批准号:
    1133795
  • 负责人:
  • 金额:
    $ 29.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-12-01 至 2016-08-31
  • 项目状态:
    已结题

项目摘要

1133795LapitskyIntellectual Merits: A fundamental study is proposed to relate the properties of multivalent counterioncrosslinked polyelectrolyte micro- and nanoparticles to their molecular interactions and formationkinetics. Currently, both their preparation and application in drug delivery largely rely on trial and error, and the literature on this subject remains limited to empirical data. While the complexation of oppositely charged polyelectrolytes has been studied for many years, detailed understanding of the particle formation process has been confounded by extremely strong binding, fast kinetics and long timescales of chain rearrangements. The formation mechanism of multivalent counterion-crosslinked polyelectrolyte particles on the other hand, (whose investigation is more tractable due to their weaker intermolecular interactions) remains virtually unexplored. Similar gaps exist in the understanding of their drug release properties, which have been (and continue to be) grossly mischaracterized by experimental methods that are unsuitable for colloidal polyelectrolyte particles. This lack of design guidelines severely limits their performance and, in cases where the drug is expensive, leads to high research and development costs.To address this, the research aims to gain a quantitative and mechanistic understanding of the parameters that govern their (1) structure, (2) stability and (3) drug encapsulation/release properties, by exploring how their colloidal properties evolve with changes in their molecular interactions. This will be achieved by probing the process of particle formation and drug encapsulation/release with an array of molecular and colloidal characterization techniques (e.g., isothermal titration calorimetry, light scattering and stopped-flow spectrofluorimetry), and analyzing the results using existing models for the formation of monodisperse colloids, adsorption and diffusion. Leveraging on the PI?s prior work on polyelectrolyte self-assembly and drug delivery, this project will yield three transformative outcomes: (1) it will provide mechanistic and quantitative guidelines for the design and application of polyelectrolyte-based colloidal drug carriers (2) it will bridge existing methods (and mechanistic models) for the preparation of monodisperse colloids from low molecular weight constituents to polyelectrolyte-based colloids and (3) it will yield important mechanistic insight into the process of micro- and nanoparticle formation from pairs of oppositely-charged polyelectrolytes, which cannot be experimentally probed in great detail directly.Broader Impacts: The project will enable development of safer, more effective and less expensive pharmaceutical products for oral, nasal and ophthalmic drug delivery. Specifically, it will establish essential guidelines for ensuring that emerging (polyelectrolyte-based) drug carriers will deliver drugs to their intended targets, and not lead to overdosing. Furthermore, the fundamental insights gained from this research could advance the design of medical and environmental diagnostics, personal care products and foods. This will be facilitated by the strong environmental engineering expertise at the University of Toledo.The project will train undergraduate, graduate and high school students in the use of materials characterization techniques, and the fundamentals of polymer, colloid and pharmaceutical science. This training will poise them for successful careers in a wide range of industries or academia. Findings from this work will be published in peer-reviewed journals and presented at professional meetings. Importantly, this work will also be integrated with the university?s outreach activities. The PI will introduce high school students to stimulus-responsive polyelectrolytes in the Engineer for a Day program that the university offers to Toledo Public Schools, and will continue his involvement in the Engineering for Teachers of Migrant Students (ETMS; CIVE 4950/5940) distance learning course. ETMS provides graduate training for teachers in rural communities who teach children of migrant farm workers, and aims to develop a set of experiments that demonstrate the importance of mathematics, science and engineering to everyday life. The PI has recently become involved with ETMS, and has already developed several demonstrations that use stimulus-responsive polymers found in household products (e.g., alginate, poly(acrylic acid), and methylcellulose) to reinforce concepts that are learned in high school chemistry.
1133795 Lapitsky智能优点:提出了一项基础研究,将多价反离子交联聚电解质微米和纳米颗粒的性质与其分子相互作用和形成动力学联系起来。目前,它们的制备和在药物释放中的应用在很大程度上依赖于试验和错误,关于这一主题的文献仍然局限于经验数据。虽然相反电荷聚电解质的络合作用已经研究多年,但由于极强的结合、快速的动力学和长时间的链重排,对颗粒形成过程的详细理解一直是混乱的。另一方面,多价反离子交联聚电解质粒子的形成机理(由于其较弱的分子间相互作用而更易于研究)实际上仍未被探索。在理解它们的药物释放特性方面也存在类似的差距,这些特性已经(并将继续)被不适合胶体聚电解质颗粒的实验方法严重错误地描述。缺乏设计指南严重限制了它们的性能,在药物昂贵的情况下,导致高昂的研发成本。为了解决这个问题,本研究旨在通过探索它们的胶体特性如何随着其分子相互作用的变化而演变,从定量和机理上了解控制它们(1)结构、(2)稳定性和(3)药物包封/释放特性的参数。这将通过使用一系列分子和胶体表征技术(例如,等温滴定量热法、光散射和停流荧光法)来探索颗粒形成和药物包埋/释放的过程,并使用现有的单分散胶体形成、吸附和扩散模型来分析结果。利用PiooS先前在聚电解质自组装和药物输送方面的工作,这个项目将产生三个变革性的结果:(1)它将为基于聚电解质的胶体药物载体的设计和应用提供机械和定量的指导;(2)它将连接现有的制备单分散胶体的方法(和机理模型),从低分子组成到基于聚电解质的胶体;以及(3)它将对由相反电荷的聚电解质对形成微米和纳米颗粒的过程提供重要的力学见解,这是无法在实验上直接探索的。布罗德影响:该项目将使开发出更安全的,更有效、更便宜的口服、鼻腔和眼科药物。具体地说,它将建立基本的指导方针,以确保新出现的(基于聚电解质的)药物载体将药物输送到预期的目标,而不会导致过量服药。此外,从这项研究中获得的基本见解可以促进医疗和环境诊断、个人护理产品和食品的设计。该项目将培训本科生、研究生和高中生使用材料表征技术,以及聚合物、胶体和制药科学的基础知识。这种培训将为他们在广泛的行业或学术界取得成功的职业生涯做好准备。这项工作的结果将发表在同行评议的期刊上,并在专业会议上公布。重要的是,这项工作还将与大学S外展活动结合起来。PI将在大学为托莱多公立学校提供的工程师日计划中向高中生介绍刺激响应性聚电解质,并将继续参与移民学生教师工程(ETMS;CIVE 4950/5940)远程学习课程。ETMS为农村社区教授农民工子女的教师提供研究生培训,旨在开发一系列实验,证明数学、科学和工程对日常生活的重要性。PI最近参与了ETMS,并已经开发了几个演示,使用家用产品(如海藻酸盐、聚丙烯酸和甲基纤维素)中的刺激响应聚合物来强化高中化学中学到的概念。

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)
Microgel and coacervate formation in polyelectrolyte​/multivalent ion mixtures
聚电解质/多价离子混合物中微凝胶和凝聚层的形成
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Yakov Lapitsky其他文献

Smart exosomes enhance PDAC targeted therapy
智能外泌体增强胰腺癌靶向治疗
  • DOI:
    10.1016/j.jconrel.2024.02.037
  • 发表时间:
    2024-04-01
  • 期刊:
  • 影响因子:
    11.500
  • 作者:
    Justin F. Creeden;Jonathan Sevier;Jian-Ting Zhang;Yakov Lapitsky;F. Charles Brunicardi;Ge Jin;John Nemunaitis;Jing-Yuan Liu;Andrea Kalinoski;Donald Rao;Shi-He Liu
  • 通讯作者:
    Shi-He Liu
Formation and structural control of surfactant and polyelectrolyte gels
  • DOI:
    10.1016/j.colsurfa.2006.01.017
  • 发表时间:
    2006-07-20
  • 期刊:
  • 影响因子:
  • 作者:
    Yakov Lapitsky;Eric W. Kaler
  • 通讯作者:
    Eric W. Kaler

Yakov Lapitsky的其他文献

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{{ truncateString('Yakov Lapitsky', 18)}}的其他基金

PFI:AIR - TT: Multifunctional Underwater Sealants with Long-Term Sustained Release Functionality
PFI:AIR - TT:具有长期持续释放功能的多功能水下密封剂
  • 批准号:
    1701104
  • 财政年份:
    2017
  • 资助金额:
    $ 29.78万
  • 项目类别:
    Standard Grant
CAREER: Photodirected Assembly of Custom-Designed Polyelectrolyte Complexes
职业:定制设计的聚电解质复合物的光导组装
  • 批准号:
    1150908
  • 财政年份:
    2012
  • 资助金额:
    $ 29.78万
  • 项目类别:
    Continuing Grant

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