Suppr超能文献

基于药代动力学的生物制剂皮下控释系统设计

Pharmacokinetics-Based Design of Subcutaneous Controlled Release Systems for Biologics.

作者信息

Grosskopf Abigail K, Ginart Antonio A, Spinosa Phillip, Shivva Vittal

机构信息

Department of Translational Pharmacokinetics and Pharmacodynamics, Genentech Inc., South San Francisco, California, USA.

Department of Electrical Engineering, Stanford University, Stanford, California, USA.

出版信息

CPT Pharmacometrics Syst Pharmacol. 2025 Apr;14(4):668-680. doi: 10.1002/psp4.13303. Epub 2025 Jan 24.

Abstract

Protein therapeutics have emerged as an exceedingly promising treatment modality in recent times but are predominantly given as intravenous administration. Transitioning to subcutaneous (SC) administration of these therapies could significantly enhance patient convenience by enabling at-home administration, thereby potentially reducing the overall cost of treatment. Approaches that enable sustained delivery of subcutaneously administered biologics offer further advantages in terms of less frequent dosing and better patient compliance. Controlled release technologies, such as hydrogels and subcutaneous implantable technologies, present exciting solutions by enabling the gradual release of biologics from the delivery system. Despite their substantial potential, significant hurdles remain in appropriately applying and integrating these technologies with the ongoing development of complex biologic-based therapies. We evaluate the potential impact of subcutaneously delivered controlled release systems on the downstream pharmacokinetics (PK) of several FDA-approved biologics by employing rigorous mathematical analysis and predictive PK simulations. By leveraging linear time-invariant (LTI) systems theory, we provide a robust framework for understanding and optimizing the release dynamics of these technologies. We demonstrate simple quantitative metrics and approaches that can inform the design and implementation of controlled release technologies. The findings highlight key opportunity areas to reduce dosing frequency, stabilize concentration profiles, and synergize the codelivery of biologics, calling for collaboration between drug delivery and PK scientists to create the most convenient, optimized, and effective precision therapies.

摘要

近年来,蛋白质疗法已成为一种极具前景的治疗方式,但主要通过静脉注射给药。将这些疗法转变为皮下(SC)给药可以通过实现居家给药显著提高患者的便利性,从而有可能降低总体治疗成本。能够实现皮下给药生物制剂持续递送的方法在减少给药频率和提高患者依从性方面具有进一步的优势。控释技术,如水凝胶和皮下植入技术,通过使生物制剂从递送系统中逐渐释放,提供了令人兴奋的解决方案。尽管它们具有巨大的潜力,但在将这些技术适当地应用并与正在进行的基于复杂生物制剂的疗法开发相结合方面,仍然存在重大障碍。我们通过采用严格的数学分析和预测性药代动力学(PK)模拟,评估皮下递送的控释系统对几种FDA批准的生物制剂下游药代动力学(PK)的潜在影响。通过利用线性时不变(LTI)系统理论,我们提供了一个强大的框架来理解和优化这些技术的释放动力学。我们展示了可以为控释技术的设计和实施提供信息的简单定量指标和方法。研究结果突出了减少给药频率、稳定浓度曲线以及协同生物制剂联合递送的关键机会领域,呼吁药物递送和PK科学家之间开展合作,以创造最方便、优化和有效的精准疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e787/12001277/d26b0a8b23a5/PSP4-14-668-g004.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验