A New In Silico Design Platform for Building Custom Controlled Release Systems

用于构建定制受控释放系统的新型计算机设计平台

• 批准号: 8394007
• 负责人: Sam N Rothstein
• 金额: $ 25.62万
• 依托单位: QRONO, INC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394007
• 关键词: Acids; Address; Adherence; Adoption; Algorithms; Animal Behavior; Animals; Antisense DNA; Behavior; Behavioral Research; Biological Assay; Biological Availability; Biomimetics; Budgets; Collaborations; Computer Simulation; Contracts; Custom; Data; Development; Drug Delivery Systems; Drug Formulations; Drug Targeting; Dyes; Environment; Evaluation; Goals; Grant; Hospitalization; Image; Immunology; Implant; In Vitro; Industry; Infusion procedures; Kidney Diseases; Kinetics; Laboratories; Left; Life; Macular degeneration; Marketing; Mathematics; Medical; Medical Research; Methods; Modeling; Motivation; Neuropeptides; Nucleic Acids; Outcome; Patient Noncompliance; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Polymers; Positioning Attribute; Preclinical Testing; Process; Production; Public Health; Pump; Quality of life; Records; Research; Research Personnel; Safety; Sales; Schedule; Scientist; Services; Small Business Technology Transfer Research; Specific qualifier value; Speed; System; Techniques; Technology; Testing; Time; Toxic effect; Universities; Validation; Vasotocin; Work; base; biodegradable polymer; commercialization; compliance behavior; controlled release; cost; cost effective; design; drug candidate; improved; in vivo; meetings; novel; phase 2 study; public health relevance; ranibizumab; relating to nervous system; small molecule; therapeutic protein; tool

DESCRIPTION (provided by applicant): Controlled release formulations can improve patient adherence and drug safety or even enable new types of basic medical research. The key to realizing these benefits is the ability to design and produce these formulations in a cost-effectiv and timely manner. Thus far, strategies at improving this process have focused on the development of novel materials and production processes that tailored for experimentally tuning a formulation's performance. Recently, the University of Pittsburgh (Pitt) has discovered new in silico design techniques that may, for the first time, make it possible to transform an expensive and time consuming empirical development process into a rapid and cost effective process. ChroKnow's long-term objective is to bring speed and efficiency formulation design process, a crucial step toward the enabling widespread adoption of controlled release systems by pharmaceutical companies and even academic laboratories. We hypothesize that algorithms (developed at Pitt) can be used to predictively design and build a diverse set of controlled release formulations based on unmet needs pharmaceutical scientists or academic researchers over a period of time that is yet unprecedented in the field. This hypothesis is supported by in vitro data demonstrating that two representative formulations have successfully been designed and produced using ChroKnow's algorithms. Herein, we put forth three real-world challenges to complete this validation: Specific Aim 1: To design and build a formulation that delivers Genentech's ranibizumab for 3 months. Motivation: Dramatically improve adherence in patients with ARMD over the current once-monthly treatment. Specific Aim 2: To create a formulation that delivers Complexa's 10-NO2-octadeca-9-enoic acid for 2 weeks. Motivation: Replicate delivery performance of osmotic pump implants current used in preclinical testing Specific Aim 3: To create a formulation for an academic PI that delivers vasotocin antisense for 10 days. Motivation: Permit the first extended evaluation of this neuropeptide's action on animal behavior in the field. Each of the formulations specified above will be designed and built in collaboration between ChroKnow Inc. and the University of Pittsburgh. Completion of each aim will yield a formulation whose in vitro release kinetics are consistent with the performance predicted by the algorithms.

描述(由申请人提供)：控释制剂可以提高患者的依从性和药物安全性，甚至可以实现新型的基础医学研究。实现这些好处的关键是有能力以具有成本效益和及时的方式设计和生产这些配方。到目前为止，改进这一过程的策略主要集中在开发新的材料和生产工艺，这些新材料和生产工艺是为实验调整配方的性能量身定做的。最近，匹兹堡大学(匹兹堡)发现了新的硅胶设计技术，这可能首次使将昂贵而耗时的经验开发过程转变为快速且经济有效的过程成为可能。ChroKnow的长期目标是提高处方设计过程的速度和效率，这是使制药公司甚至学术实验室能够广泛采用控释系统的关键一步。我们假设，算法(在PIT开发)可以用来预测性地设计和建立一套多样化的控释配方，在一段时间内，基于未得到满足的需求，制药科学家或学术研究人员在该领域还是前所未有的。这一假设得到了体外数据的支持，该数据表明，使用ChroKnow的算法成功地设计和生产了两个具有代表性的配方。在此，我们提出了三个现实世界的挑战来完成这一验证：具体目标1：设计和制造一种能在3个月内提供基因泰克的ranibizumab的配方。动机：与目前每月一次的治疗相比，ARMD患者的依从性显著提高。具体目标2：创建一种制剂，提供Complexa的10-NO2-十八碳-9-烯酸2周。动机：复制目前临床前测试中使用的渗透泵植入物的输送性能特定目标3：为学术PI创造一种可输送血管催产素反义10天的配方。动机：首次对这种神经肽在野外动物行为中的作用进行扩展评估。上面规定的每一种配方都将由ChroKnow Inc.和匹兹堡大学合作设计和制造。每个目标的完成将产生一个其体外释放动力学与算法预测的性能一致的配方。