1. Advancements in Programmable Lipid Nanoparticles: A Comprehensive Review of the Four-Domain Model for Precision Drug Delivery
- Author
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Liu, Zhaoyu, Chen, Jingxun, Xu, Mingkun, Gracias, David H., Yong, Ken-Tye, Wei, Yuanyuan, and Ho, Ho-Pui
- Subjects
Quantitative Biology - Biomolecules ,Physics - Biological Physics - Abstract
Programmable lipid nanoparticles (LNPs) represent a critical advancement in drug delivery. It offers precise spatiotemporal control over drug distribution and release, which is essential for treating complex diseases such as cancer and genetic disorders. However, the design and understanding of these sophisticated systems necessitate a structured framework. This review introduces a novel Four-Domain Model - the Architecture, Interface, Payload, and Dispersal - providing a modular perspective that emphasizes the programmability of LNPs. We delve into the dynamics between LNPs components and their environment throughout their lifecycle, focusing on thermodynamic stability during synthesis, storage, delivery, and drug release. Through these four distinct but interconnected domains, we introduce the concept of input stimuli, functional components, and output responses. This modular approach offers new perspectives for the rational design of programmable nanocarriers for exquisite control over payload release while minimizing off-target effects. Advances in bioinspired design principles could lead to LNPs that mimic natural biological systems, enhancing their biocompatibility and functionality. This review summarizes recent advancements, identifies challenges, and offers outlooks for programmable LNPs, emphasizing their potential to evolve into more intelligent, naturally integrated systems that enhance scalability and reduce side effects. Additionally, exploring innovative anatomical routes such as intranasal and intraocular delivery holds significant promise for enhancing drug delivery efficacy and patient compliance, further expanding the clinical potential of programmable LNPs., Comment: 53 pages, 9 figures
- Published
- 2024