Introduction:
LipidBrick LNPs – Revolutionizing Nucleic Acid Therapeutics – In the ever-evolving landscape of nucleic acid therapeutics, the delivery mechanism plays a pivotal role in determining the success of treatments. Enter LipidBrick®, a groundbreaking range of cationic lipids developed by Polyplus®, poised to redefine the game in lipid nanoparticle (LNP) formulations. This blog explores the technical intricacies of LipidBrick® and its implications for advancing the field of DNA and RNA therapeutics.
LipidBrick®: A Game-Changing Innovation
Polyplus® takes centre stage as an innovator in nucleic acid delivery, presenting LipidBrick®, a family of cationic lipids designed exclusively for LNP formulation. These active lipids, based on an imidazolium polar head, usher in a new era of possibilities for prophylactic and therapeutic vaccines, allowing a seamless transition between ready-to-use reagents and custom LNP formulations.
Tailoring LNPs to Perfection
Recognizing the diverse nature of genetic materials, applications, and target tissues, Polyplus® emphasizes the need for a wide variety of lipids to modulate the physico-chemical properties of LNPs. LipidBrick® rises to the occasion, ensuring therapeutic success by offering a spectrum of formulations tailored to specific needs, applications, and organ targets.
LipidBrick® IM21.7c: The Hero of the Story
Within the LipidBrick® library, LipidBrick® IM21.7c takes centre stage as the cationic lipid used in the formulation of jetMESSENGER® and in vivo–jetRNA®+, providing a fine-tuned LNP formulation. Its unique structure, protected by an independent patent, showcases Polyplus®’ commitment to pushing the boundaries of nucleic acid delivery.
Proof-of-Concept Study: Illuminating the Potential
Polyplus® conducted a proof-of-concept study using Luciferase mRNA to demonstrate the potential of LipidBrick® IM21.7c in mRNA-LNP formulation. The study compared LipidBrick®-based LNPs with traditional ionizable lipids, showcasing superior particle size, zeta potential, and 100% mRNA encapsulation efficiency.
In Vivo Efficiency and Biodistribution: A Paradigm Shift
LNPs’ properties not only influence mRNA delivery efficiency but also dictate their in vivo biodistribution. Polyplus® engineered LipidBrick®-based LNPs to exhibit a different biodistribution pattern than those formulated with ionizable lipids. The result? Enhanced mRNA delivery to the lungs and spleen, with reduced accumulation in the liver.
Stability Matters: Ensuring Patient Safety: LipidBrick LNPs
Patient safety and drug efficacy hinge on LNP stability. Polyplus® subjected its cLNP formulation with LipidBrick® IM21.7c to a rigorous 3-month stability test, revealing exceptional stability and sustained mRNA expression when stored at 4°C. This underscores the reliability of LipidBrick®-based LNPs for clinical applications.
Safety Assessment: A Clean Bill of Health
To address concerns about potential pro-inflammatory responses, Polyplus® conducted a comparative study between LipidBrick® IM21.7c and the validated ionizable lipid (Dlin-MC3-DMA) in mice. The results? LipidBrick®-based LNPs exhibited a similar cytokine profile to those with ionizable lipids, indicating minimal to no pro-inflammatory response.
LNPs’ properties not only influence mRNA delivery efficiency but also dictate their in vivo biodistribution. Polyplus® engineered LipidBrick®-based LNPs to exhibit a different biodistribution pattern than those formulated with ionizable lipids. The result? Enhanced mRNA delivery to the lungs and spleen, with reduced accumulation in the liver.
Stability Matters: Ensuring Patient Safety
Patient safety and drug efficacy hinge on LNP stability. Polyplus® subjected its cLNP formulation with LipidBrick® IM21.7c to a rigorous 3-month stability test, revealing exceptional stability and sustained mRNA expression when stored at 4°C. This underscores the reliability of LipidBrick®-based LNPs for clinical applications.
Safety Assessment: A Clean Bill of Health
Polyplus® undertook a comparative study investigating potential pro-inflammatory reactions between LipidBrick® IM21.7c and the established ionizable lipid, Dlin-MC3-DMA, in mice.
The findings revealed that LipidBrick®-based LNPs showcased a cytokine profile akin to those formulated with ionizable lipids.
This similarity strongly suggested minimal to negligible pro-inflammatory responses.
This study underscores LipidBrick® IM21.7c’s potential as a promising alternative in nanoparticle-based formulations, offering comparable outcomes to established ionizable lipids while potentially mitigating concerns related to inflammatory reactions, a significant advancement in drug delivery system development.
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