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

描述（由申请人提供）：控释制剂可以提高患者依从性和药物安全性，甚至可以进行新型基础医学研究。实现这些效益的关键是以具有成本效益和及时的方式设计和生产这些配方的能力。到目前为止，改进这一过程的策略集中在开发新材料和生产工艺上，这些材料和生产工艺专门用于实验调整配方的性能。最近，匹兹堡大学（皮特）发现了新的计算机设计技术，这可能是第一次，使人们有可能将昂贵和耗时的经验开发过程转化为快速和具有成本效益的过程。ChroKnow的长期目标是实现快速高效的配方设计过程，这是制药公司甚至学术实验室广泛采用控释系统的关键一步。我们假设算法（在Pitt开发）可用于预测性地设计和构建一组不同的控释制剂，这些制剂基于制药科学家或学术研究人员在一段时间内未满足的需求，这在该领域是前所未有的。这一假设得到了体外数据的支持，这些数据表明，使用ChroKnow算法成功设计和生产了两种代表性制剂。在此，我们提出了三个现实世界的挑战，以完成这一验证：具体目标1：设计和建立一个配方，提供基因泰克的雷珠单抗3个月。 动机：与目前每月一次的治疗相比，大大提高了ARMD患者的依从性。具体目标2：创造一种制剂，可持续2周递送Complexa的10-NO2-十八碳-9-烯酸。 动机：目前用于临床前试验的渗透泵植入物的重复递送性能具体目标3：为学术PI创建递送10天的反义血管催产素的制剂。 动机：允许在该领域对这种神经肽对动物行为的作用进行首次扩展评估。上述每种配方将由ChroKnow Inc.和匹兹堡大学。每个目标的完成将产生其体外释放动力学与算法预测的性能一致的制剂。

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.