Ionizable Lipids Customization

CD Formulation specializes in tailoring ionizable lipids to meet the unique needs of our clients. With integrated expertise in lipid chemistry, analytical characterization, formulation development and preclinical testing, we offer comprehensive customization options to optimize key properties like transfection efficiency, pharmacokinetics, and scalability.

What are Ionizable Lipids?

Ionizable lipids can respond to pH changes in endosomes or lysosomes, converting from a neutral state to a positively charged state in an acidic environment. Ionizable lipids in their neutral state are relatively stable and can be formulated and stored efficiently. Positively charged ionizable lipids promote cellular uptake and endosomal escape.

Molecular structures and component segments of ionizable lipids (Xu Y.; et al. 2023)

What Can We Do for Ionizable Lipids Development?

• Ionizable Polymer Lipids Development

CD Formulation has extensive experience in the development of ionizable polymer-lipids, which enhance particle formation and exhibit a preference for transfecting specific cell populations. We specialize in addressing the complexity of these lipids and overcoming the challenges associated with toxic polycation cores and non-degradable backbones.

• Biodegradable Ionizable Lipids Development

We use strategies such as ester and disulfide bonds to enhance biodegradability, optimize the balance between activity and degradation, and meet the critical need to reduce side effects and accumulation. Through careful synthesis and formulation, we are able to efficiently deliver RNA therapeutics, ASOs, and CRISPR/Cas9 systems.

• Branched-Tail Ionizable Lipids Development

We can customize advanced branched-tail ionizable lipids for targeted mRNA delivery applications. Through medicinal chemistry and screening, we develop novel lipids containing branches near the headgroup or at the end of tails to optimize transfection activity and hepatocyte targeting.

• Unsaturated Ionizable Lipids Development

In order to enhance gene delivery, we develop unsaturated ionizable lipids with varying fluidity and efficacy. As experts in designing and testing these lipids, we ensure effective therapeutic outcomes by optimizing membrane disruption, payload release, and in vivo RNA delivery.

Our Combinatorial Chemistry Methods for Ionizable Lipid Library Development

• Michael addition
• Ring-opening epoxides with amines
• Reductive amination of aldehydes
• Multicomponent reactions
• Enzyme-assisted chemical reactions

Applications of Our Customized Ionizable Lipids

• mRNA Vaccines

Our ionizable lipids can enhance mRNA delivery and protein expression for the development of more effective vaccines, leveraging the immune activation of self-amplifying mRNA constructs.

• Drug Delivery Systems

We customize ionizable lipids to optimize the efficiency and performance of lipid nanoparticle formulations, supporting the delivery of a variety of small molecule and biologic therapeutics.

• Nucleic Acid Delivery

Our ionizable lipids enable efficient intracellular transport of genes, gene editing tools, and oligonucleotides, facilitating applications in gene therapy through regulated expression, silencing, or genomic editing.

• T-cell Engineering

Our formulation expertise aids in developing ionizable lipids tailored for chimeric antigen receptor mRNA delivery and T-cell genetic modification, enhancing adoptive cellular immunotherapy approaches.

Why Choose Our Ionizable Lipids Customization Services?

• The pH-sensitive protonatable or ionizable lipids we developed have emerged as the most promising class of lipids for efficient intracellular nucleic acid delivery.
• We optimize ionizable lipids so that they not only bind nucleic acids well, but also quickly ionize to release the nucleic acids once they reach the appropriate site.
• With a deep understanding of the endocytosis process, we control ionizable lipids to protonate and bind to phospholipids in the acidic environment of the endosome, destabilizing the endosomal membrane and allowing cargo to escape the endosome.

Contact us today to discuss how we can leverage our formulation expertise to help you achieve your research and therapeutic goals! Our scientists are ready to collaborate and advance your lipid-based delivery technology.