DOTAP and the blood–brain barrier: Advancing siRNA delivery with cationic lipids
At Avanti Research™, we believe that reliable, high-purity lipids are the foundation of scientific breakthroughs. One of our most trusted and versatile molecules—DOTAP (1,2-dioleoyl-3-trimethylammonium-propane)—recently played a key role in a study that tackled one of the toughest challenges in drug delivery: transporting siRNA across the blood–brain barrier (BBB).
This newly published study by Cheng and Kandimalla focused on developing lipid-based RNA delivery systems that can target brain endothelial cells. Using a formulation of cationic bicelles composed of our DPPC, DHPC, and DOTAP lipids, the team demonstrated effective siRNA delivery in a human in vitro BBB model.
Why DOTAP is a go-to cationic lipid for siRNA delivery
As a permanently charged cationic lipid, DOTAP excels at forming stable electrostatic complexes with negatively charged RNA, including siRNA and mRNA. This property is essential for protecting nucleic acids during delivery and promoting uptake into target cells.
But DOTAP’s benefits go beyond binding. In this study, it enabled the formation of cationic bicelles—discoidal nanostructures with enhanced membrane interaction and faster cellular uptake compared to traditional liposomes. These bicelles were internalized into brain endothelial cells through multiple pathways, including clathrin-mediated endocytosis, caveolin-mediated uptake, and lipid raft-associated mechanisms.
That multi-pathway access increases delivery efficiency, which is especially valuable for hard-to-reach tissues like the brain.
DOTAP supports endosomal escape—A key step in RNA delivery
Once inside the cell, the challenge becomes endosomal escape. Many delivery systems fail at this step, trapping siRNA in lysosomes before it can reach the cytosol.
Here’s where DOTAP shines again.
The study found that while the bicelles themselves localized in early and late endosomes, the siRNA was able to escape and avoid lysosomal degradation—suggesting that DOTAP played a role in disrupting endosomal membranes and promoting RNA release. This mechanism, often called the flip-flop effect, is crucial for therapeutic success in lipid-based RNA delivery platforms.
Proven performance across RNA delivery applications
DOTAP has been trusted for decades by researchers worldwide. It’s highly effective in a variety of systems—liposomes, lipid nanoparticles (LNPs), and now cationic bicelles. Its predictable performance, ease of formulation, and proven ability to facilitate transfection and intracellular delivery make it a top choice in the field.
For researchers developing neurotherapeutics, gene silencing agents, or RNA vaccines, choosing a lipid like DOTAP means choosing a high-performance reagent with a track record of success.
Available from Avanti Research™
At Avanti Research, we offer DOTAP in multiple package sizes and formats—each batch manufactured to exacting standards and with detailed documentation. Whether you're developing delivery systems for preclinical studies or scaling up your next big idea, our team is here to support your success.
This latest study is a powerful reminder of what’s possible when cutting-edge formulation meets reliable lipid chemistry. With DOTAP, researchers are pushing past barriers—literally—and moving closer to transformative RNA-based therapies for conditions like Alzheimer’s disease.