CL1 & Analogs for Drug Delivery

CL1 & Analogs for Drug Delivery

Published by BroadPharm on January 23, 2024

CL1 is a novel trialkyl ionizable lipid crucial for creating Lipid Nanoparticles (LNPs). These LNPs act as carriers, encapsulating and delivering siRNA, mRNA, DNA, or small molecules into cells.

Figure 1. Structure of CL1

CL1 demonstrates superior mRNA delivery to the liver compared to many other ionizable lipids in existing literature. CL1, ALC-0315, and SM-102 exhibit comparable expression levels at the injection site, surpassing those of older generation benchmark lipids (DLinDMA, KC2, MC3). Additionally, CL1 and ALC-0315 demonstrate elevated expression in the liver, while SM-102 exhibits lower expression, resembling MC3 more closely. CL1 is a versatile lipid suitable for both systemic therapeutic and intramuscular vaccine applications, effectively delivering a variety of nucleic acid payloads (K. Lam).

BroadPharm's Offerings

In order to enhance and optimize LNP drug delivery, BroadPharm has introduced a range of CL1 analogs. These analogs feature diverse modifications to the chargeable amine head for precise fine-tuning of CL1-LNP properties. As demonstrated below...

One head modification is represented by BP Lipid 310 (Structure A), where ethanolamine is linked to a polyunsaturated hydrophobic tail via an ester bond. The presence of the terminal hydroxyl group enhances hydrogen-bonding interactions with nucleic acids, potentially enhancing the capacity for transfection.

Structure A

The next head modification is exemplified by BP Lipid 323 (Structure B), where azetidine, a rigid 4-member ring, and a polyunsaturated hydrophobic tail are linked by an ester bond.

Structure B

Another modification of the head is represented by BP Lipid 321 (Structure C), where 3-hydroxyazetidine, a water-soluble hydroxyl group attached to the azetidine ring, is linked to a polyunsaturated hydrophobic tail through an ester bond.

Structure C

Finally, in BP Lipid 322 (Structure D), 1-(2-Hydroxyethyl)piperazine, a water-soluble hydroxyl group attached to a multicharged piperazine moiety that may allow for the administration of repeated doses of LNP with increased effectiveness and safety (Kim M), is linked to a polyunsaturated hydrophobic tail through an ester bond.

Structure D

Lipid supplier and customer synthesis

As a leading drug delivery lipid supplier worldwide, BroadPharm offers a wide array of ionizable lipids, PEG lipids, phospholipids, and helper lipids. BroadPharm also provides fast speed custom synthesis of novel lipid molecules to empower your advanced research.

Journal References

K. Lam, A. Leung, A. Martin, M. Wood, P. Schreiner, L. Palmer, O. Daly, W. Zhao, K. McClintock, J. Heyes, Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications. Adv. Mater. 2023, 35, 2209624.

Kim M, Jeong M, Lee G, et al. Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. Bioeng Transl Med. 2023; 8(6):e10556. doi:10.1002/btm2.10556