Advancements in Programmable Lipid Nanoparticles: Exploring the Four-Domain Model for Targeted Drug Delivery

TL;DR

This paper reviews the latest advancements in programmable lipid nanoparticles, introducing a Four-Domain Model to enhance targeted drug delivery, addressing manufacturing, regulatory, and novel administration routes, and comparing artificial LNPs with natural exosomes.

Contribution

It proposes a novel Four-Domain Model for LNPs, providing a modular framework to analyze their mechanism and programmability for improved targeted drug delivery.

Findings

Introduces a Four-Domain Model for LNP analysis

Examines innovative administration routes like intranasal and intraocular

Compares artificial LNPs and natural exosomes in functionality

Abstract

Programmable lipid nanoparticles, or LNPs, represent a breakthrough in the realm of targeted drug delivery, offering precise spatiotemporal control essential for the treatment of complex diseases such as cancer and genetic disorders. In order to provide a more modular perspective and a more balanced analysis of the mechanism, this review presents a novel Four-Domain Model that consists of Architecture, Interface, Payload, and Dispersal Domain. We explored the dynamical equilibrium between LNPs components and the surroundings throughout their destiny, from formulation to release. On the basis of this, we delve deep into manufacturing challenges, scalability issues, and regulatory hurdles, associated with the clinical translation of LNP technology. Within the framework focusing on the programmability in each domain, we prioritized patient-centric factors like dosing regimens, administration techniques, and potential consequences. Notably, this review expands to innovative anatomical routes, such as intranasal and intraocular administration, offering a thorough examination of the advantages and disadvantages of each route. We also offered a comprehensive comparison between artificial LNPs and natural exosomes in terms of functionality, biocompatibility, and therapeutic potential. Ultimately, this review highlights the potential of programmable LNPs to evolve into more intelligent, naturally integrated systems, achieving optimal biocompatibility and functionality.