Lipid-based drug delivery systems are transforming how we approach the formulation and delivery of modern therapeutics. They offer promising solutions to long-standing challenges in drug solubility, targeting, and stability. In a recent ACS/CAS webinar, experts from CAS, AstraZeneca, and The Ohio State University explored the current landscape and future directions of lipid-based drug delivery. Access the webinar recording here to learn how lipid technologies are shaping the future of pharmaceuticals.

Highlights from the webinar

Dr. Qiongqiong Angela Zhou started the webinar presenting a comprehensive analysis of lipid-based drug delivery systems, derived from over 200,000 scientific journals and patents in the CAS Content Collection™. She highlighted the advantages of lipid carriers, including improved solubility for hydrophobic drugs, enhanced targeting through surface modifications, and protection from immune clearance. Angela also shared insights into the chemical landscape of lipids, including phospholipids, steroids, and functionalized lipids, and discussed their roles in various delivery formats such as liposomes, micelles, and solid lipid nanoparticles (LNPs).

Angela emphasized the commercial and clinical relevance of lipid systems, showcasing patent trends, disease applications (notably cancer and infectious diseases), and the synthesis pathways of key lipids. She concluded by encouraging researchers to explore the full CAS report for deeper insights.

Dr. Annette Bak continued the presentation focusing on real-world applications of lipids in drug discovery and development. She categorized lipid drug delivery systems into emulsions, vesicular systems, and particulate carriers and discussed their use in enhancing solubility, prolonging circulation, and enabling targeted delivery.  

Annette shared case studies from AstraZeneca’s pipeline, including the use of lipid-based formulations to improve the bioavailability of poorly soluble small molecules like PROTACs, and the oral delivery of biologics such as antisense oligonucleotides (ASOs). She also discussed the central role of LNPs in delivering mRNA and gene-editing tools, particularly in vaccines and liver-targeted therapies. She also addressed the challenges of targeting tissues beyond the liver and shared strategies for modifying lipid composition and protein corona formation to achieve extrahepatic delivery.  

She concluded by encouraging researchers to balance innovation with simplicity, noting that while lipid systems offer powerful capabilities, their success depends on thoughtful design, manufacturability, and regulatory feasibility.

Dr. Robert Lee from The Ohio State University concluded the presentation with an academic and industrial perspective on liposomes and lipid nanoparticles. He reviewed FDA-approved liposomal drugs like Doxil and Onivyde, highlighting their design, manufacturing complexities, and therapeutic benefits. Bob also discussed the evolution of LNPs for mRNA delivery, including their structural characteristics, formulation strategies, and production methods such as microfluidics and impingement jet mixing.

He introduced his own research on QTsomes^TM, a five-component LNP system designed for improved targeting and endosomal escape. Bob emphasized the importance of understanding lipid geometry, charge, and formulation parameters to optimize delivery and reduce off-target effects. He ended by highlighting the challenges of large-scale manufacturing.

To wrap up the webinar, the speakers answered many audience questions, everything from the role and function of lipids in drug delivery to what types of drugs they can deliver. Questions about their limitations and outlook were also answered.

Key questions from the webinar:

What is the role of branched-chain lipids in drug delivery?

Branched-chain lipids, prominently used in COVID-19 vaccines, play a vital role in enhancing drug delivery. Angela explained they improve membrane fluidity and facilitate transfection by helping lipid nanoparticles fuse more effectively with cell membranes. They also stabilize nanoparticles during production, preventing premature degradation or aggregation. Annette added that the degree of branching is a key parameter in structure-activity relationship studies when designing novel ionizable lipids. Bob emphasized the importance of lipid geometry, noting that branched lipids promote the formation of non-bilayer phases, which are essential for endosomal escape.

How do lipid nanoparticles improve drug delivery efficiency?

Bob highlighted that lipid nanoparticles are especially critical for mRNA delivery, as mRNA cannot be chemically stabilized to the same extent as oligonucleotides. LNPs encapsulate and protect mRNA from degradation and facilitate its cellular uptake and endosomal escape. Annette noted that while mRNA can be delivered without LNPs, the efficiency is extremely low and typically requires direct injection into the target tissue. Angela added that LNPs also benefit small molecule drugs, especially hydrophobic ones like PROTACs, by improving solubility and bioavailability.

Can lipid-based systems deliver highly potent drugs like those used in pancreatic cancer?

Yes. Bob cited Onivyde (liposomal irinotecan) as a successful example used in pancreatic cancer. Liposomes can reduce toxicity and improve pharmacokinetics, making them ideal for potent drugs with narrow therapeutic windows. However, he cautioned that for low-potency drugs, the required lipid dose may be too high for clinical use.

What is the function of cholesterol in lipid nanoparticles?

Cholesterol is essential for stabilizing lipid bilayers and modulating membrane fluidity. Angela explained that it enhances the mobility of embedded molecules and supports transfection. Bob added that cholesterol helps eliminate phase transitions in lipid membranes and may aid in liver targeting by attracting low-density lipoproteins. Annette noted that while cholesterol improves delivery, it can also affect formulation stability, so a balance must be struck.

Are exosomes a viable alternative to liposomes?

While exosomes are naturally derived and offer biocompatibility, they face significant challenges in scalability, reproducibility, and regulatory approval. Angela noted that liposomes are easier to produce and control. Annette added that exosomes are complex biologics with high variability, making them difficult to standardize with Bob agreeing, pointing out that exosomes are still in early stages of development and face greater regulatory hurdles.

Are lipid nanoparticles, polymeric nanoparticles, or hybrids the future of advanced drug delivery?

All three have a role. Annette sees utility in both lipid and polymer systems, depending on the application. For mRNA delivery, lipids are currently favored due to lower toxicity. Angela highlighted the CAS analysis on hybrid systems that combine lipids with polymers or inorganic materials for enhanced functionality. Bob added that polyethylene glycol (PEG) itself is a polymer, making many LNPs inherently hybrid systems. He also emphasized the biocompatibility of natural lipids as a key advantage.

Learn more 

Read about the full CAS report on lipids in drug delivery to explore a snapshot of the detailed data, trends, and insights. Access the webinar recording and slides here.